Epilepsija yra sud\u0117tinga paroksizmin\u0117 neurologin\u0117 patologija, kuriai b\u016bdingi pasikartojantys traukuliai. \u0160i liga yra gana da\u017ena\u00a0\u2013 ja serga apie 0,7\u00a0proc. populiacijos\u00a0[1\u20133]. Kofeinas yra labiausiai pasaulyje vartojamas centrin\u0117s nerv\u0173 sistemos (CNS) stimuliatorius [4]. Atsi\u017evelgiant \u012f jo stimuliuojam\u0105j\u012f poveik\u012f, nenuostabu, kad epilepsija sergantys \u017emon\u0117s ir sveikatos prie\u017ei\u016bros paslaug\u0173 teik\u0117jai stebi ir tiria, ar kofeinas gali sukelti traukulius [5]. \u0160iandien tr\u016bksta duomen\u0173, kurie leist\u0173 vienareik\u0161mi\u0161kai atsakyti \u012f \u0161\u012f klausim\u0105. Straipsnyje ap\u017evelgiami naujausi \u012frodymai apie kofeino poveik\u012f traukuliams\u00a0[6].<\/p>\n
\u00a0<\/p>\n
Kofeino veikimas<\/b><\/p>\n
Nustatyta, kad kofeinas (1,3,7-trimetilksantinas) ma\u017eina nuovarg\u012f ir padidina budrum\u0105, reakcijos greit\u012f, informacijos apdorojim\u0105, susijaudinim\u0105 ir motorin\u0119 veikl\u0105. Kofeino poveik\u012f grei\u010diausiai lemia jo s\u0105veika su \u012fvairiais neuromediatoriais, o svarbiausia\u00a0\u2013 su adenozinu [7]. Adenozinas, prisijungdamas prie receptori\u0173, skatina mieg\u0105 ir ma\u017eina smegen\u0173 \u017eiev\u0117s jaudrum\u0105\u00a0[8,\u00a09]. Kadangi molekulin\u0117 kofeino strukt\u016bra yra pana\u0161i \u012f adenozin\u0105, kofeinas taip pat gali jungtis prie adenozino A1 ir A2A receptori\u0173, tokiu b\u016bdu neleisdamas adenozinui prisijungti\u00a0\u2013 veikia kaip adenozino antagonistas. Kofeinas s\u0105veikauja su kitu svarbiu slopinan\u010diu neuromediatoriumi\u00a0\u2013 gama aminosviesto r\u016bg\u0161timi (GABA), modifikuodamas GABA-A receptorius\u00a0[10\u201312]. Adenozinui aktyvinant A1 receptorius, slopinama dopamino\u00a0neuromediatoriaus, kuris yra susij\u0119s su susikaupimu ir motyvacija, ir glutamato sekrecija. Taigi kofeinas didina dopamino ir glutamato i\u0161siskyrim\u0105, slopina GABA, sukeldamas stimuliuojam\u0105j\u012f poveik\u012f [13, 14].<\/p>\n
\u00a0<\/p>\n
Klinikiniai atvejai<\/b><\/p>\n
Keliuose klinikini\u0173 atvej\u0173 prane\u0161imuose teigiama, kad kofeinas gali sukelti traukulius epilepsija sergantiems \u017emon\u0117ms. Nustatyta, kad traukuliai pasirei\u0161k\u0117 pavartojus labai dideles (toksi\u0161kas) kofeino dozes arba po to, kai ilgesn\u012f laik\u0105 buvo vartojamas kofeinas [15\u201327]. Viename atvejo apra\u0161yme minima moteris, kuri tur\u0117jo kelet\u0105 status epilepticus <\/i>(SE) epizod\u0173, pasirei\u0161kian\u010di\u0173 savaitgaliais [27]. Ji penktadieniais\u2013sekmadieniais reguliariai i\u0161gerdavo beveik 2\u00a0l kavos, o darbo dienomis\u00a0\u2013 apie 0,5\u00a0l kavos. Savaitgaliais nustojusi gerti kav\u0105, ji patyr\u0117 ma\u017eiau traukuli\u0173 ir nebetur\u0117jo SE epizod\u0173 [27]. Kitame atvejyje nurodoma, kad vyrui, kuriam per savait\u0119 buvo ma\u017eiausiai 6 fokaliniai vaistams atspar\u016bs priepuoliai, nustojus gerti daugiau nei 2\u00a0l kavos per dien\u0105, i\u0161nyko priepuoliai [25]. Prane\u0161ama apie vyr\u0105, sergant\u012f generalizuota epilepsija, kuris nevartojo vaist\u0173 nuo traukuli\u0173, ta\u010diau jo priepuoliai pasikartojo, kai jis prad\u0117jo dideliais kiekiais gerti \u0161alt\u0105j\u0105 arbat\u0105 su kofeinu. Traukuli\u0173 suma\u017e\u0117jo nutraukus kofeino vartojim\u0105 [27]. Taip pat yra prane\u0161im\u0173 apie priepuolius i\u0161g\u0117rus energini\u0173 g\u0117rim\u0173 [28]. Nustatyta, kad kofeinas prailgina traukulius po elektrokonvulsin\u0117s terapijos, skiriamos gydant sunki\u0105 depresij\u0105 [29].<\/p>\n
\u00a0<\/p>\n
Kofeino poveikio traukuliams klinikiniai tyrimai<\/b><\/p>\n
Kofeino \u012ftakos traukuliams klinikini\u0173 tyrim\u0173 yra tik keletas. Vieno j\u0173 metu buvo apklausiami \u017emon\u0117s, atvykstantys \u012f ligonin\u0119 po priepuolio. J\u0173 buvo klausiama apie \u012fprast\u0105 kofeino vartojim\u0105 [30]. Vidutini\u0161kai kavos suvartojimas dien\u0105 prie\u0161 priepuol\u012f neb\u016bdavo didesnis, nei \u012fprastinis suvartojimas dienomis be priepuoli\u0173. Ma\u017edaug dviem tre\u010ddaliams buvo diagnozuota epilepsija. \u0160iame pogrupyje buvo tendencija vartoti ma\u017eiau kofeino prie\u0161 traukulius [30]. Vadinasi, nustojus vartoti kofeino, galima inicijuoti kai kuri\u0173 epilepsijos form\u0173 traukulius.<\/p>\n
Kituose 2 didel\u0117s imties anketiniuose tyrimuose buvo tiriamas ilgalaikis kofeino vartojimo poveikis traukuliams ir epilepsijai. Pirmajame tyrime buvo \u012fvertinti keli sveikatos ir gyvenimo b\u016bdo parametrai, \u012fskaitant epilepsij\u0105, traukulius ir kofeino vartojim\u0105 [31]. Prane\u0161usi\u0173 apie traukulius ar epilepsij\u0105 tiriam\u0173j\u0173 kofeino suvartojamas kiekis nesiskyr\u0117 nuo visos tiriam\u0173j\u0173 grup\u0117s. Antrasis tyrimas \u012fvertino, ar kofeino poveikis gimdai tur\u0117jo \u012ftakos kar\u0161\u010diavimo priepuoli\u0173 i\u0161sivystymui. Tyrimas atliktas naudojant klausimyn\u0105 apie gyvenimo b\u016bd\u0105 n\u0117\u0161tumo metu. Buvo apklausta daugiau nei 35\u00a0t\u016bkst. moter\u0173, kurioms buvo teikiamos antenatalin\u0117s paslaugos Danijoje [32]. Motinos kofeino vartojimas n\u0117\u0161tumo metu netur\u0117jo \u012ftakos kar\u0161\u010diavimo priepuoli\u0173 rizikai per pirmuosius 3 gyvenimo m\u0117nesius.<\/p>\n
Nei\u0161ne\u0161iotiems k\u016bdikiams kofeino citratas gali b\u016bti naudojamas siekiant pagerinti baltosios med\u017eiagos mikrostrukt\u016bros vystym\u0105si. Atsitiktin\u0117s atrankos, kontroliuojamame tyrime k\u016bdikiams buvo skiriama arba standartin\u0117 30\u00a0mg\/kg doz\u0117, arba didel\u0117 80\u00a0mg\/kg kofeino citrato doz\u0117\u00a0[33]. Didel\u0119 doz\u0119 vartojusi\u0173 pacient\u0173 grup\u0117je, palyginti su standartin\u0119 doz\u0119 vartojusiaisiais, buvo nustatytas nereik\u0161mingas traukuli\u0173 skai\u010dius ir trukm\u0117s padid\u0117jimas. Vaistas nuo traukuli\u0173 fenitoinas padidino kofeino klirens\u0105, o vidutinis kofeino pusin\u0117s eliminacijos laikas suma\u017e\u0117jo beveik 50\u00a0proc. Karbamazepinas ir valproin\u0117 r\u016bg\u0161tis netur\u0117jo \u012ftakos kofeino metabolizmui [34].<\/p>\n
\u00a0<\/p>\n
Tyrimai su gyv\u016bnais <\/b><\/p>\n
Tyrimuose su \u017eiurk\u0117mis, pel\u0117mis, triu\u0161iais, j\u016br\u0173 kiaulyt\u0117mis, kat\u0117mis, \u0161unimis nustatyta, kad didel\u0117s kofeino doz\u0117s padidina smegen\u0173 jaudrum\u0105 ir sukelia traukulius bei encefalopatij\u0105 [35]. Kai traukulius sukelia kiti veiksniai, tokie kaip pentilenetetrazolis (PTZ), kofeinas taip pat suma\u017eina traukuli\u0173 pasirei\u0161kimo slenkstin\u0119 rib\u0105 [36\u201339].<\/p>\n
\u00a0<\/p>\n
\u012erodyta, kad \u017eiurki\u0173 pateli\u0173, kurioms n\u0117\u0161tumo metu duota kofeino (doz\u0117mis, prilygstan\u010diomis \u017emoni\u0173 suvartojamiems 3\u20134 puodeliams kavos per dien\u0105), palikuonys yra jautresni priepuoliams, sukeliamiems hipertermijos ar flurotilo, palyginti su kontroline grupe, kuriai buvo skiriamas tik vanduo [40, 41]. Kofeinu paveiktiems jaunikliams buvo atid\u0117ta GABA-ergini\u0173 neuron\u0173 migracija \u012f hipokamp\u0105, o kontrolin\u0117je grup\u0117je to nepasteb\u0117ta. \u0160is u\u017edelstas migravimas siejamas su bendru neuron\u0173 tinklo jaudrumo padid\u0117jimu [40]. Kitame tyrime nustatyta adenozino A1, A2A ir GABA-A receptori\u0173 mRNR ekspresijos poky\u010di\u0173 tarp \u017eiurki\u0173 jaunikli\u0173, kurie gimdoje buvo veikiami kofeino, palyginti su kontroline grupe [42].<\/p>\n
\u00a0<\/p>\n
Teigiamas kofeino poveikis gyv\u016bnams<\/b><\/p>\n
Kai kuri\u0173 atlikt\u0173 tyrim\u0173 su gyv\u016bnais duomenimis, kofeinas gali tur\u0117ti nuo epilepsijos ir traukuli\u0173 apsaugant\u012f poveik\u012f. \u012erodyta, kad, ilg\u0105 laik\u0105 veikiant jaunus grau\u017eikus ma\u017eomis kofeino doz\u0117mis, suma\u017e\u0117ja jautrumas traukuliams. Viename tyrime \u017eiurk\u0117ms buvo skiriamas kofeinas pirm\u0105j\u0105 savait\u0119 po gimimo, kartu buvo leid\u017eiama ir 1 i\u0161 5 traukulius provokuojan\u010di\u0173 med\u017eiag\u0173\u00a0\u2013 PTZ, pikrotoksino, bikukulino, strichnino ar kainin\u0117s r\u016bg\u0161ties (kainato), kol pasirei\u0161k\u0117 pirmieji miokloniniai tr\u016bk\u010diojimai. Palyginti su kontrolin\u0117mis grup\u0117mis, \u017eiurki\u0173 jaunikli\u0173, veikiam\u0173 kofeinu, priepuolio riba buvo 20\u201340\u00a0proc. didesn\u0117 veikiant PTZ, pra\u0117jus 28 dienoms po gimimo. 42 dien\u0173 am\u017eiaus \u017eiurk\u0117ms, kurioms buvo duota kofeino, priepuoli\u0173 slenkstis padid\u0117jo 40\u201350\u00a0proc., palyginti su kontrolin\u0117mis grup\u0117mis. Suaugusioms \u017eiurk\u0117ms (70\u201390 dien\u0173), vartojusioms kofein\u0105, reik\u0161mingai padid\u0117jo PTZ ir kaino r\u016bg\u0161ties traukuli\u0173 riba, palyginti su kontrolin\u0117mis grup\u0117mis [43].<\/p>\n
Kitame tyrime pasteb\u0117ta, kad, ilg\u0105 laik\u0105 skiriant ma\u017eas kofeino dozes 7\u201311 dien\u0173 po gimimo, reik\u0161mingai padid\u0117ja generalizuot\u0173 tonini\u0173 ir klonini\u0173 traukuli\u0173 priepuoli\u0173 slenkstis, bet mioklonini\u0173 tr\u016bk\u010diojim\u0173 ar minimali\u0173 klonini\u0173 priepuoli\u0173 slenks\u010di\u0173 poky\u010di\u0173 nenustatyta [44]. Vartojant PTZ, ma\u017ea kofeino doz\u0117 suma\u017eino \u012f traukulius pana\u0161i\u0173 epizod\u0173 da\u017en\u012f, sutrumpino j\u0173 trukm\u0119, priklausomai nuo doz\u0117s [47].<\/p>\n
Fenobarbitalis \u2013 da\u017eniausiai vartojamas vaistas nuo traukuli\u0173 naujagimi\u0173 priepuoliams gydyti, ta\u010diau galintis sukelti neurodegeneracij\u0105 [48]. Buvo atliktas kofeino neuroprotekcini\u0173 savybi\u0173 \u012fvertinimo tyrimas, siekiant atrasti b\u016bd\u0105, kaip u\u017ekirsti keli\u0105 fenobarbitalio sukeltai degeneracijai. \u017diurki\u0173 jaunikliai 3 dienas i\u0161 eil\u0117s (pradedant 4 diena po gimimo) vartojo fenobarbital\u012f su kofeinu arba be jo. \u017diurk\u0117ms, gavusioms tik fenobarbital\u012f, nustatyta padid\u0117jusi l\u0105steli\u0173 \u017e\u016btis smegenyse. Kartu vartojusioms kofein\u0105 \u017eiurki\u0173 smegenyse to nepasteb\u0117ta. Teigiama, kad kofeinas ma\u017eina u\u017edegimini\u0173 citokin\u0173 kiek\u012f, neurotoksi\u0161kum\u0105 bei kovoja su fenobarbitalio sukelt\u0173 A1 ir A2A receptori\u0173 suma\u017e\u0117jimu [48]. Nustatyta, kad veikiant \u017eiurki\u0173 jauniklius kofeinu kartu su etanoliu, padid\u0117ja jautrumas priepuoliams (sukeliamiems PTZ), o veikiant tik kofeinu (be etanolio) pasirei\u0161k\u0117 apsauginis poveikis [49].<\/p>\n
\u00a0<\/p>\n
Kofeino poveikis suaugusiems grau\u017eikams<\/b><\/p>\n
Galimo kofeino apsauginio poveikio nuo traukuli\u0173 ir epilepsijos suaugusiems gyv\u016bnams tyrim\u0173 rezultatai yra \u012fvair\u016bs. Viename tyrime nenustatyta jokio l\u0117tinio, ma\u017e\u0173 kofeino dozi\u0173 poveikio traukuliams, kuriuos suk\u0117l\u0117 pikrotoksinas arba kainin\u0117 r\u016bg\u0161tis, palyginti su kontroline grupe [50]. Kitame tyrime nustatyta, kad gyv\u016bnams, kelias dienas vartojusiems kofeino, palyginti su fiziologinio tirpalo injekcijomis, traukuli\u0173 trukm\u0117 buvo daug trumpesn\u0117 [51]. \u0160i\u0173 dviej\u0173 tyrim\u0173 rezultatai gali b\u016bti paai\u0161kinti metodologiniais skirtumais, \u012fskaitant skirtingus kofeino vartojimo b\u016bdus ir skirting\u0173 priepuolius provokuojan\u010di\u0173 med\u017eiag\u0173 naudojim\u0105.<\/p>\n
Kitame tyrime intrakranijini\u0173 elektroencefalografijos (EEG) bang\u0173 skai\u010dius ir trukm\u0117 \u017eiurk\u0117ms suma\u017e\u0117jo po vienos vidutin\u0117s kofeino doz\u0117s, palyginti su pradiniu rodikliu. Tyrime nebuvo nustatyta jokio ilgalaikio kofeino vartojimo poveikio [52]. Naujesnio tyrimo metu nustatytas intrakranijini\u0173 EEG bang\u0173 skai\u010diaus ir trukm\u0117s suma\u017e\u0117jimas pavartojus kofeino, manoma, susij\u0119s su citokinais IL-6 ir NFkB [53]. \u017diurk\u0117ms, patyrusioms sunk\u0173 traumin\u012f smegen\u0173 su\u017ealojim\u0105, vienkartin\u0117 kofeino doz\u0117 sutrumpino epilepsijos epizod\u0105 [54]. Ai\u0161k\u0117ja, kad kofeinas turi neuroapsaugin\u012f poveik\u012f nuo traukuli\u0173 ankstyvuoju gyvenimo laikotarpiu ir po traumini\u0173 smegen\u0173 su\u017ealojim\u0173. Poveikis priklauso nuo am\u017eiaus, traukulius skatinan\u010di\u0173 med\u017eiag\u0173, traukuli\u0173 modelio, kofeino doz\u0117s ir vartojimo b\u016bdo.<\/p>\n
\u00a0<\/p>\n
Kofeino ir vaist\u0173 nuo traukuli\u0173 s\u0105veika gyv\u016bn\u0173 tyrimuose<\/b><\/p>\n
Informacijos apie kofeino ir vaist\u0173 nuo traukuli\u0173 s\u0105veik\u0105 gyv\u016bn\u0173 organizme yra pakankamai daug. Daugelyje publikuot\u0173 tyrim\u0173, siekiant \u012fvertinti kofeino vartojimo poveik\u012f antikonvulsini\u0173 vaist\u0173 savyb\u0117ms, priepuoliams sukelti buvo naudojamas maksimalus elektro\u0161okas [56\u201362]. \u017diurk\u0117ms buvo \u0161virk\u0161\u010diama kofeino ir vieno i\u0161 \u0161i\u0173 vaist\u0173 nuo traukuli\u0173: karbamazepino, fenitoino, fenobarbitalio, valproin\u0117s r\u016bg\u0161ties, felbamato, okskarbazepino, lamotrigino, tiagabino, gabapentino ir topiramato. Vienos doz\u0117s kofeino injekcijos suma\u017eino traukuli\u0173 slenkst\u012f ir padidino fenobarbitalio, karbamazepino, fenitoino, topiramato, gabapentino, valproin\u0117s r\u016bg\u0161ties ir felbamato kiek\u012f, reikaling\u0105 50\u00a0proc. \u017eiurki\u0173 apsaugoti nuo elektros sukelt\u0173 traukuli\u0173, bet vartojant okskarbazepin\u0105, lamotrigin\u0105 ir tiagabin\u0105 poky\u010di\u0173 nepasteb\u0117ta [56\u201358, 60\u201362]. Kai kofeinas buvo skiriamas ilg\u0105 laik\u0105, fenobarbitalio, karbamazepino, fenitoino, topiramato, gabapentino ir valproin\u0117s r\u016bg\u0161ties kiekis, reikalingas apsaugoti 50\u00a0proc. \u017eiurki\u0173 nuo traukuli\u0173, taip pat padid\u0117jo, ta\u010diau v\u0117l poky\u010di\u0173 nebuvo stebima vartojant okskarbazepin\u0105, lamotrigin\u0105 ir tiagabin\u0105 [57, 59\u201362]. Kit\u0173 tyrim\u0173, kuriuose naudojami kiti epilepsijos suk\u0117limo modeliai, pavyzd\u017eiui, naudojant PTZ ar ritmin\u0119 vestibulin\u0119 stimuliacij\u0105, rezultatai taip pat atitiko \u0161iuos duomenis [63]. Kofeinas gerokai suma\u017eino PTZ kiek\u012f, reikaling\u0105 traukuliams sukelti, palyginti su druskos tirpalu [38]. Diazepamas padidino PTZ sukeliam\u0173 traukuli\u0173 slenkst\u012f. Kai diazepamas ir kofeinas buvo vartojami kartu, diazepamo antikonvulsinis poveikis susilpn\u0117jo.<\/p>\n
Kofeino ir vaist\u0173 nuo traukuli\u0173 s\u0105veikos poveikis gali pasireik\u0161ti dviem skirtingais lygmenimis. Kadangi kofeinas nepakeit\u0117 fenobarbitalio, klonazepamo, fenobarbitalio, valproin\u0117s r\u016bg\u0161ties, karbamazepino, gabapentino, topiramato ir etosuksimido koncentracijos, manoma, kad jis gali veikti kaip \u0161i\u0173 vaist\u0173 antagonistas [39, 58, 61, 62]. Paprastesnis farmakodinamin\u0117s kofeino ir vaist\u0173 nuo traukuli\u0173 s\u0105veikos paai\u0161kinimas\u00a0\u2013 kofeinas didina jautrum\u0105 traukuliams, netiesiogiai padidindamas vaist\u0173 poreik\u012f, tod\u0117l jis yra analogi\u0161kas kitoms traukulius sukelian\u010dioms med\u017eiagoms.<\/p>\n
Kofeinas tam tikru mastu veikia visus vaistus nuo traukuli\u0173, topiramatas stipriausiai s\u0105veikauja su kofeinu. Palyginti vienkartin\u0119 kofeino doz\u0119 su kartotiniu kofeino vartojimu, s\u0105veikos su vaistais nuo traukuli\u0173 skirtumo nebuvo nustatyta, i\u0161skyrus su karbamazepinu (s\u0105veika su kofeinu buvo stipresn\u0117, kai kofeinas buvo skiriamas ilg\u0105 laik\u0105) [6].<\/p>\n
\u00a0<\/p>\n
Patofiziologiniai kofeino poveikio traukuliams mechanizmai<\/b><\/p>\n
Jautrumas traukuliams priklauso nuo smegen\u0173 jaudrumo, kuriam \u012ftak\u0105 turi genetika, strukt\u016brin\u0117s anomalijos, vidiniai (pvz., hormonai, miegas) ir i\u0161oriniai veiksniai (pvz., mityba). Tyrimo su geneti\u0161kai mutavusiomis pel\u0117mis duomenimis, genetiniai veiksniai gali daryti \u012ftak\u0105 tam, kaip kofeinas veikia traukulius [65]. Naujausiuose tyrimuose teigiama, kad kofeinas gali sukelti epigenetinius poky\u010dius, turin\u010dius \u012ftak\u0105 neuron\u0173 jaudrumui, kurie gali b\u016bti epileptogenez\u0117s pagrindas [66]. Miego tr\u016bkumas yra nepriklausomas priepuoli\u0173 suk\u0117l\u0117jas, ta\u010diau pati epilepsija gali b\u016bti miego sutrikdymo prie\u017eastis [67\u201369]. Kofeinas ma\u017eina nuovarg\u012f ir slopina mieg\u0105 skatinan\u010dius procesus, tod\u0117l kofeino poveikis traukuliams gali b\u016bti susij\u0119s su jo \u012ftaka miegui [4, 9]. D\u0117l epilepsijos ir traukuli\u0173 suma\u017e\u0117j\u0119s arba neoptimalus miego kiekis gali padidinti kofeino vartojim\u0105 ir padidinti jautrum\u0105 traukuliams.<\/p>\n
Ankstyvieji tyrimai rodo, kad kofeinas trukdo procesams, kurie nutraukia elektrini\u0173 traukuli\u0173 veikl\u0105 [70]. In vitro<\/i> tyrim\u0173 rezultatai rodo, kad kofeinas padidina tarpl\u0105stelinio kalcio i\u0161siskyrim\u0105. Tai yra susij\u0119 su didesniu traukuli\u0173 aktyvumu d\u0117l padid\u0117jusio neuron\u0173 jaudrumo [71\u201373]. Pana\u0161iai kofeinas gali palengvinti traukulius keisdamas kalio sroves, sukelian\u010dias ma\u017eiau neigiam\u0105 membranos potencial\u0105 ir jungdamasis su endogeninio tarpl\u0105stelinio adenozino inhibitoriniu A1 receptoriaus potipiu [74\u201376]. Naujausi atradimai rodo, kad adenozino A2a receptoriai gali b\u016bti \u012ftraukti \u012f patogenez\u0119, tai paai\u0161kint\u0173 nuo doz\u0117s priklausom\u0105 kofeino poveik\u012f [77].<\/p>\n
Adenozinas daro \u012ftak\u0105 traukuli\u0173 baig\u010diai ir depresijai po gimdymo, kontroliuoja laisvuosius radikalus\u00a0[78\u201382]. Ilgalaikis ma\u017e\u0173 kofeino dozi\u0173 poveikis gali tur\u0117ti neuroprotekcin\u012f poveik\u012f kei\u010diant A1 ir A2 receptori\u0173 tank\u012f ir jautrum\u0105 adenozinui ir kofeinui [54, 83\u201387]. \u0160is poveikis priklauso nuo srities ir nuo am\u017eiaus [83\u201385, 88]. Kofeino poveikis ankstyvuoju gyvenimo laikotarpiu gali tur\u0117ti daugiau apsauginio poveikio nei suaugusiesiems, grei\u010diausiai tod\u0117l, kad jaunesnio am\u017eiaus \u017emon\u0117ms vykta daugiau A receptori\u0173 tankumo poky\u010di\u0173 [83\u201385, 88].<\/p>\n
\u00a0<\/p>\n
Metodologijos \u012ftaka<\/b><\/p>\n
Daugiausiai tyrim\u0173 su gyv\u016bnais duomenys rodo, kad kofeinas gali padidinti jautrum\u0105 traukuliams arba apsaugoti nuo j\u0173. Poveikis priklauso nuo doz\u0117s, vartojimo tipo (vienkartin\u0117 doz\u0117 ar ilgalaikis vartojimas) bei nuo vystymosi stadijos, kurios metu prad\u0117tas vartoti kofeinas. Kai kuri\u0173 tyrim\u0173 su gyv\u016bnais rezultatai yra prie\u0161taringi. Taip gal\u0117jo nutikti d\u0117l naudojamos skirtingos metodikos, skirting\u0173 epilepsijos tip\u0173, skirting\u0173 priepuoli\u0173 suk\u0117limo ir kofeino vartojimo b\u016bd\u0173 ir d\u0117l nevienod\u0173 kofeino ar chemini\u0173 konvulsant\u0173 dozi\u0173 [50\u201352, 58, 70, 90]. Kai kuri\u0173 tyrim\u0173 im\u010di\u0173 dyd\u017eiai yra ma\u017ei, ribojantys j\u0173 patikimum\u0105 [38, 39]. Tyrim\u0173 su gyv\u016bnais i\u0161vad\u0173 pritaikymas \u017emon\u0117ms yra didelis i\u0161\u0161\u016bkis, nes kofeino metabolizmas \u017emon\u0117ms ir gyv\u016bnams yra skirtingas. Iki \u0161iol tyrim\u0173 su gyv\u016bnais rezultatai nebuvo pakartoti klinikini\u0173 tyrim\u0173 metu ir provokuojantis ar apsauginis kofeino poveikis traukuliams \u017emon\u0117ms nepasteb\u0117tas [30\u201333]. Tyrim\u0173 metu gal\u0117jo pasitaikyti neatitikim\u0173 tarp kofeino vartojimo matavimo vienet\u0173 [30\u201332, 67].<\/p>\n
\u00a0<\/p>\n
Apibendrinimas <\/b><\/p>\n
Tyrimai su gyv\u016bnais rodo, kad kofeinas gali padidinti jautrum\u0105 traukuliams, ta\u010diau neai\u0161ku, kaip \u0161ie atradimai gali b\u016bti pritaikyti \u017emon\u0117ms. Nustatyta, kad kofeinas gali s\u0105veikauti su keliais vaistais nuo traukuli\u0173, labiausiai su topiramatu. Kol n\u0117ra patikim\u0173 klinikini\u0173 tyrim\u0173, vienintel\u0117 pagr\u012fsta rekomendacija gydytojams, pasteb\u0117jusiems kofeino vartojimo poky\u010dius, padariusius \u012ftak\u0105 traukuliams ar farmakoterapinei epilepsijai, informacijos \u012ftraukimas \u012f paciento ligos istorij\u0105. Svarbu, kad kofeinas b\u016bt\u0173 laikomas veiksniu, galin\u010diu veikti traukuli\u0173 kontrol\u0117s u\u017etikrinim\u0105 ir palaikym\u0105.<\/p>\n
STRAIPSNIO AUTOR\u0116 \u2013\u00a0<\/strong>Andra Ker\u0161evi\u010di\u016bt\u0117,\u00a0Lietuvos sveikatos moksl\u0173 universitetas<\/b><\/p>\n <\/b><\/p>\n Literat\u016bra<\/b><\/p>\n 1. Forsgren L, Beghi E, \u00d5un A, Sillanp\u00e4\u00e4 M. The epidemiology of epilepsy in Europe – a systematic review. Eur J Neurol. 2005;12: 245\u201353. Epilepsija yra sud\u0117tinga paroksizmin\u0117 neurologin\u0117 patologija, kuriai b\u016bdingi pasikartojantys traukuliai. \u0160i liga yra gana da\u017ena\u00a0\u2013 ja serga apie 0,7\u00a0proc. populiacijos. Kofeinas yra labiausiai pasaulyje vartojamas centrin\u0117s nerv\u0173 sistemos (CNS) stimuliatorius. Atsi\u017evelgiant \u012f jo stimuliuojam\u0105j\u012f poveik\u012f, nenuostabu, kad epilepsija sergantys \u017emon\u0117s ir sveikatos prie\u017ei\u016bros paslaug\u0173 teik\u0117jai stebi ir tiria, ar kofeinas gali sukelti traukulius.<\/p>\n","protected":false},"author":1,"featured_media":146,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[27313],"tags":[26706,26673,9117,12334,26692,26700,26709,26695,26681,881,12758,26689,26472,26717,26730,26729,26711,26721,26456,26683,26693,26713,26705,26708,26699,18884,26677,26685,10802,26716,26688,26682,26684,26690,12756,26710,26719,411,26723,10799,26725,26722,40,13846,26712,26697,26715,26726,26727,26704,26718,26671,26678,26669,26675,26686,26676,26672,26703,11857,10823,26701,26691,26698,26679,11864,10771,26714,26702,12781,10824,26674,18913,26687,26670,26680,10751,26694,26724,26707,26728,26696,26720,5990,10790],"site":[27309],"post_item_type":[28490],"class_list":["post-145","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-gydymo-naujienos","tag-absence","tag-actions","tag-adenozinas","tag-adult","tag-affects","tag-afterdischarges","tag-altered","tag-alters","tag-anesth","tag-antagonistas","tag-antagonists","tag-antiepileptic","tag-behav","tag-biochem","tag-biochem-behav","tag-caffeine-exposure","tag-chroscinska","tag-clonic","tag-consumption","tag-convulsive","tag-cortical","tag-czuczwar","tag-damage","tag-death","tag-developing","tag-different","tag-differential","tag-discharges","tag-during","tag-electroshock","tag-epilepsia","tag-epileptic","tag-epileptiform","tag-experimental","tag-exposure","tag-gasior","tag-generalized","tag-health","tag-hippocampal","tag-intake","tag-involvement","tag-kindled","tag-kofeinas","tag-kontrolinemis","tag-krawczyk","tag-kubova","tag-maximal","tag-mechanisms","tag-memory","tag-model","tag-mouse","tag-nehlig","tag-neurochem","tag-neurol","tag-neurons","tag-neurophysiol","tag-neuroreport","tag-neurosci","tag-neurotox","tag-occurrence","tag-onset","tag-pentylenetetrazol","tag-phenobarbital","tag-postnatal","tag-postpartum","tag-prevent","tag-prolonged","tag-protective","tag-protects","tag-receptors","tag-reduces","tag-regulation","tag-relation","tag-samsonsen","tag-sander","tag-seizure","tag-should","tag-shows","tag-slices","tag-sudden","tag-synaptotoxicity","tag-tchekalarova","tag-tonic","tag-tyrimai","tag-withdrawal","site-imunitetas-lt"],"acf":{"post_sites":[27309]},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/posts\/145","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/comments?post=145"}],"version-history":[{"count":0,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/posts\/145\/revisions"}],"acf:term":[{"embeddable":true,"taxonomy":"site","href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/site\/27309"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/media\/146"}],"wp:attachment":[{"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/media?parent=145"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/categories?post=145"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/tags?post=145"},{"taxonomy":"site","embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/site?post=145"},{"taxonomy":"post_item_type","embeddable":true,"href":"https:\/\/www.pasveik.lt\/lt\/wp-json\/wp\/v2\/post_item_type?post=145"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
2. MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain. 2000;123:665\u201376.
3. Sander JW. The epidemiology of epilepsy revisited. [Curr Opin Neurol. 2003] – PubMed result. Curr Opin Neurol. 2003;16:165\u2013 70.
4. Nehlig A. Are we dependent upon coffee and caffeine? A review on human and animal data. Neurosci Biobehav Rev. 1999;23:563\u201376.
5. Nehlig A. Effects of coffee\/caffeine on brain health and disease: what should i tell my patients? Pract Neurol. 2016;16:89\u201395.
6. van Koert RR, et al. Caffeine and seizures: a systematic review and quantitative analysis. Epilepsy Behav. 2018;80:37\u201347. https:\/\/doi.org\/10.1016\/j. yebeh.2017.11.003.
7. Fredholm BB, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999;51(1):83\u2013133.
8. Brundege J, Dunwiddie T. Metabolic regulation of endogenous adenosine release from single neurons. Neuroreport. 1998;9: 3007\u201311.
9. Huang ZL, Urade YHO. The role of adenosine in the regulation of sleep. Curr Top Med Chem. 2011;11:1047\u201357.
10. Roca D, Schiller G, Farb D. Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid\/benzodiazepine receptor site interactions. Mol Pharmacol. 1988;33:481\u20135.
11. Watanabe M, et al. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol. 2002;213:1\u201347.
12. Hossain S, et al. Effects of coffee components on the response of GABA(a) receptors expressed in Xenopus oocytes. J Agric Food Chem. 2003;51:7568\u201375.
13. Borycz J, et al. Differential glutamate-dependent and glutamate-independent adenosine A1 receptor-mediated modulation of dopamine release in different striatal compartments. J Neurochem. 2007;101:355\u201363.
14. Solinas M, et al. Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J Neurosci. 2002;22(15):6321\u20134.
15. Banner W, Czaijka P. Acute caffeine overdose in the neonate. Am J Dis Child. 1980;134(5):495\u20138.
16. Mueller SM, Solow EB. Seizures associated with a new combination \u201c pick-me-up \u201d pill. Ann Neurol. 1982;11(3):322. Curr Neurol Neurosci Rep (2019) 19: 32 Page 5 of 7 32
17. Bolton V, Leicht C, Scanlon T. Postpartum seizure after epidural blood patch and intravenous caffeine sodium benzoate. Anesthesiology. 1989;70:146\u20139.
18. Cohen SM, Laurito CE, Jo Curran M. Grand mal seizure in a post-partum patient following intravenous infusion of caffeine sodium benzoate to treat persistent headache. J Clin Anesth. 1992;4:48\u201351.
19. Paech M. Unexpected postpartum seizures associated with postdural puncture headache treated with caffeine. Int J Obstet Anesth. 1996;5(1):43\u20136.
20. Iyadurai SJP, Chung SS. New-onset seizures in adults: possible association with consumption of popular energy drinks. Epilepsy Behav. 2007;10:504\u20138.
21. Chang I, et al. Seizures in a night club. Lancet. 2007;370(9583):220.
22. Babu KM, et al. First-onset seizure after use of 5-hour. Energy. 2011;27:539\u201340.
23. Kaufman K, Sachdeo R. Caffeinated beverages and decreased seizure control. Seizure. 2003;12:519\u201321.
24. Antonaci F, et al. Epileptic seizure during aspirin and caffeine withdrawal in a drug induced headache. Funct Neurol. 1996;11:333\u20137.
25. Bonilha L, Li LM. Heavy coffee drinking and epilepsy. Seizure. 2004;13:284\u20135.
26. Maiga D, Seyni H, Sidikou A, Azouma A. Convulsive crisis in tramadol and caffeine abusers: about 8 cases and review of the literature. Pan Afr Med J. 2012;13:24.
27. Mackow MJ, et al. Increased caffeine intake leads to worsening of electrocorticographic epileptiform discharges as recorded with a responsive neurostimulation device. Clin Neurophysiol. 2016;127: 2341\u20132.
28. Borron SW, et al. Energy drink exposures reported to Texas poison centers: analysis of adverse incidents in relation to total sales, 2010\u20132014. Regul Toxicol Pharmacol. 2018;97:1\u201314.
29. Hinkle P, et al.. Use of caffeine to lengthen seizures in ECT. Am J Psychiatry. 1997;144: 1143\u20138.
30. Samsonsen C, et al. Is dietary caffeine involved in seizure precipitation? Epilepsy Behav. 2013;28:147\u201350.
31. Dworetzky B, et al. A prospective study of smoking, caffeine, and alcohol as risk factors for seizures or epilepsy in young adult women: data from NUrses\u2019 health study II. Epilepsia. 2010;51(2):198\u2013205.
32. Vestergaard M, et al. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures. Pediatrics. 2005;116:1089\u201394.
33. Vesoulis ZA, et al. Early high-dose caffeine increases seizure burden in extremely preterm neonates: a preliminary study. J Caffeine Res. 2016;6(3):101\u20137.
34. Wietholtz H, et al. Effect of phenytoin , carbamazepine , and valproic acid on caffeine metabolism. Eur J Clin Pharmacol. 1989;36:401\u20136.
35. Chu N. Caffeine- and aminophylline-induced seizures. Epilepsia. 1981;22:85\u201394.
36. L\u00f6scher W, Schmidt D. Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res. 1988;2:145\u201381.
37. Cutrufo C, et al. Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study. Eur J Pharmacol. 1992;222:1\u20136.
38. Goto M, Morishita S, Fukuda H. Anticonvulsant action of diazepam in mice pretreated with caffeine. J Pharmacobiodyn. 1983;6: 654\u20139.
39. Luszczki J, et al. (2006) Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice. Pharmacol Rep. 2006;58(5):652\u20139.
40. Silva CG, et al. Adenosine receptor antagonists including caffeine alter fetal brain development in mice. Sci Transl Med. 2013;5:197ra104.
41. Fazeli W, et al. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice. Exp Neurol. 2017;295:88\u2013103 This study shows the effects of early caffeine exposure on the brain.
42. Ad\u00e9n U, et al. Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the rat brain. Pediatr Res. 2000;48:177\u201383.
43. Guillet R. Neonatal caffeine exposure alters seizure susceptibility in rats in an age-related manner. Dev Brain Res. 1995;89:124\u20138.
44. Tchekalarova J, Kubov\u00e1 H, Mare\u0161 P. Effects of postnatal caffeine exposure on seizure susceptibility in developing rats. Brain Res. 2007;1150:32\u20139.
45. Tchekalarova J, Kubov\u00e1 H, Mare\u0161 P. Postnatal period of caffeine treatment and time of testing modulate the effect of acute caffeine on cortical epileptic afterdischarges in rats. Brain Res. 2010;1356: 121\u20139.
46. Tchekalarova J, Kubov\u00e1 H, Mare\u0161 P. Effects of caffeine on cortical epileptic afterdischarges in adult rats are modulated by postnatal treatment. Acta Neurol Belg. 2013;113:493\u2013500.
47. Tchekalarova J, Kubov\u00e1 H, Mare\u0161 P. Postnatal caffeine treatment affects differently two pentylenetetrazol seizure models in rats. Seizure. 2009;18:463\u20139.
48. Endesfelder S, et al.. Caffeine protects against anticonvulsant-induced impaired neurogenesis in the developing rat brain. Neurotox Res. 2018;34:173\u201387 This study shows the effects of early caffeine exposure.
49. Matovu D, Alele PE. Seizure vulnerability and anxiety responses following chronic co-administration and acute withdrawal of caffeine and ethanol in a rat model. J Basic Clin Physiol Pharmacol. 2018;29:1\u201310.
50. Hoexter MQ, et al.. Consequences of prolonged caffeine administration and its withdrawal on pilocarpine- and kainate-induced seizures in rats. Epilepsia. 2005;46:1401\u20136.
51. Souza MA, Mota BC, Gerbatin RR, Rodrigues FS, Castro M, Fighera MR, et al. Antioxidant activity elicited by low dose of caffeine attenuates pentylenetetrazol-induced seizures and oxidative damage in rats. Neurochem Int. 2013;62:821\u201330.
52. Germ\u00e9 K, et al. Effect of caffeine and adenosine receptor ligands on the expression of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Epilepsy Res. 2015;110:105\u201314.
53. Dede F, et al. Antagonism of adenosinergic system decrease SWD occurrence via an increment in thalamic NFkB and IL-6 in absence epilepsy. J Neuroimmunol. 2019;326:1\u20138.
54. Lusardi TA, et al.. Caffeine prevents acute mortality after TBI in rats without increased morbidity. Exp Neurol. 2012;234:161\u20138.
55. Faingold CL, et al.. Susceptibility to seizure-induced sudden death in DBA\/2 mice is altered by adenosine. Epilepsy Res. 2016;124:49\u201354 This study links adenosine to sudden death.
56. Gasior M, et al. Felbamate demonstrates low propensity for 32 Page 6 of 7 Curr Neurol Neurosci Rep (2019) 19: 32 interaction with methylxanthines and Ca 2 q channel modulators against experimental seizures in mice. Eur J Pharmacol. 1998;352: 207\u201314.
57. Chro\u015bci\u0144ska-Krawczyk M, Jargiello M, Czuczwar S. Influence of caffeine on the protective action of some conventional and novel antiepileptic drugs. Pharmacol Rep. 2007;59:118 Abstract.
58. Czuczwar SJ, et al.. Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice. Epilepsia. 1990;31(3):318\u201323.
59. Gasior M, et al.. Chronic caffeine and the anticonvulsant potency of antiepileptic drugs against maximal electroshock. Pharmacol Biochem Behav. 1996;54:639\u201344.
60. Chro\u015bci\u0144ska-Krawczyk M, et al. Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2009;61:819\u201326.
61. Gasior M, et al.Anticonvulsant activity of phenobarbital and valproate against maximal electroshock in mice during chronic treatment with caffeine and caffeine discontinuation. Epilepsia. 1996;37:262\u20138.
62. Chro\u015bci\u0144ska-Krawczyk M, et al.. Influence of caffeine on the protective activity of gabapentin and topiramate in a mouse model of generalized tonic-clonic seizures. Pharmacol Rep. 2016;68:680\u20135 Important animal study on the interaction between antiseizure drugs and caffeine.
63. Hashiguchi W, et al.. Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizure-susceptible EL mice. Psychiatry Clin Neurosci. 2001;55:319\u201324.
64. Kulkarni C, Joseph T, David J. Inhibition of anticonvulsant action of carbamazepine by aminophylline and caffeine in rats. Indian J Exp Biol. 1989;27(12):1048\u201351.
65. Seale TW, et al.. Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice. Pharmacol Biochem Behav. 1987;26:381\u20137.
66. Williams-Karnesky RL, et al. Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis. J Clin Invest. 2013;123:3552\u201363.
67. Samsonsen C, et al.. The impact of sleep loss on the facilitation of seizures: a prospective case-crossover study. Epilepsy Res. 2016;127:260\u20136.
68. Bazil CW. Sleep and epilepsy. Semin Neurol. 2017;37:407\u201312.
69. Derry C, Duncan S. Sleep and epilepsy. Epilepsy Behav. 2013;26: 394\u2013404.
70. Albertson TE, Joy R, Stark L. Caffeine modification of kindled amygdaloid seizures. Pharmacol Biochem Behav. 1983;19:339\u201343.
71. Chen T-H, Lee B, Yang C, Hsu WH. Effects of caffeine on intracellular calcium release and calcium influx in a clonal\u03b2-cell line RINm5F. Life Sci. 1996;58:983\u201390.
72. Angehagen M, et al. Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport. 2003;14:471\u20135.
73. Andersen P, Bliss T, Skrede K. Unit analysis of hippocampal polulation spikes. Exp Brain Res. 1971;13:208\u201321.
74. Harinath S, Sikdar SK. Inhibition of human TREK-1 channels by caffeine and theophylline. Epilepsy Res. 2005;64:127\u201335.
75. Ault B, et al. Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy. Brain Res. 1987;426:93\u2013102.
76. Moraidis I, Bingmann D. Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (Guinea pig). Brain Res. 1994;640:140\u2013 5.
77. Esmaili Z, Heydari A. Effect of acute caffeine administration on PTZ-induced seizure threshold in mice: involvement of adenosine receptors and NO-cGMP signaling pathway. Epilepsy Res.2019;149:1\u20138.
78. Boison D. Adenosine and seizure termination: endogenous mechanisms. Epilepsy Curr. 2013;13:35\u20137.
79. Whitcomb K, et al.. Adenosine involvement in postictal events in amygdala-kindled rats. Epilepsy Res. 1990;6:171\u20139.
80. Almeida C, et al.. Adenosine promotes neuronal recovery from reactive oxygen species induced lesion in rat hippocampal slices. Neurosci Lett. 2003;339:127\u201330.
81. Kov\u00e1cs R, et al. Free radical\u2013mediated cell damage after experimental status epilepticus in hippocampal slice cultures. J Neurophysiol. 2002;88:2909\u201318.
82. Go\u0142embiowska K, Dziubina A. The effect of adenosine A(2A) receptor antagonists on hydroxyl radical, dopamine, and glutamate in the striatum of rats with altered function of VMAT2. Neurotox Res. 2012;22:150\u20137.
83. Rigoulot M-A, et al.. Prolonged low-dose caffeine exposure protects against hippocampal damage but not against the occurrence of epilepsy in the lithium-pilocarpine model in the rat. Epilepsia. 2003;44:529\u201335.
84. Conlay LA, et al. Caffeine alters plasma adenosine levels. Nature. 1997;389:136.
85. Johansson B, Ahlberg S. Effect of long term caffeine treatment on A1 and A2 adenosine receptor binding and on mRNA levels in rat brain. Naunyn Schmiedeberg’s Arch Pharmacol. 1993;347:407\u201314.
86. Duarte J, et al. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10\/LTJ mice. PLoS One. 2012;7:e21899.
87. Cognato G, et al. Caffeine and an adenosine A2A receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life. J Neurochem. 2010;112: 453\u201362.
88. Neville HJ, Bavelier D. Specificity and plasticity in neurocognitive development in humans. Director, Jefferson Headache Center, 111 South 11th St., Suite 8130, Philadelphia, PA 19107. 2000.
89. Ferr\u00e9 S. An update on the mechanisms of psychostimulant effects of caffeine. J Neurochem. 2008;105:1067\u201379.
90. Kostopoulos G, et al. Caffeine blocks absence seizures in the tottering mutant mouse. Epilepsia. 1987;28: 415\u201320.<\/p>\n","protected":false},"excerpt":{"rendered":"