Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia

Shuaib, Ashfaq; Ijaz, Sadiq; Hasan, S. M. Nazmul; Kalra, Jawahar

doi:10.1016/0006-8993(92)91076-q

Cited by 88 publications

(23 citation statements)

References 42 publications

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“…Vigabatrin showed protection of the hippocampal CA1 region and substantia nigra reticulata in a gerbil model of repetitive forebrain ischemia. 27 Tiagabine significantly reduced the ischemic-induced elevation of glutamate levels in CA1 area during the postischemic period and protected the CA1 pyramidal cell layer in a gerbil model of transient ischemia. 28,29 In these in vivo experiments, however, postischemic hypothermia occurred, and it may have played a role in the obtained results.…”

Section: Discussionmentioning

confidence: 99%

Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia

Costa

Leone

Saulle

et al. 2004

Stroke

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Background and Purpose-The possible neuroprotective effect of endogenous ␥-aminobutyric acid (GABA) on the irreversible electrophysiological changes induced by in vitro ischemia on striatal neurons was investigated. In particular, the aim of the study was the characterization of the neuroprotective action of 2 antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA transaminase. Methods-Extracellular field potential recordings were obtained from rat corticostriatal slice preparations. In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose was omitted and oxygen was replaced with N 2 . Results-An irreversible loss of the field potentials recorded from striatal neurons was observed after 10 minutes of ischemia in control solution. Conversely, tiagabine and vigabatrin partially prevented the ischemia-induced field potential loss. Surprisingly, both GABA A and GABA B receptor antagonists blocked these effects. Accordingly, neuroprotection could be obtained only when GABA A and GABA B receptor agonists were coapplied, but not when a single agonist was given in isolation. Key Words: anticonvulsants Ⅲ corpus striatum Ⅲ electrophysiology Ⅲ ischemia Ⅲ receptors, GABA C ombined oxygen and glucose deprivation is a wellestablished in vitro model of ischemia for electrophysiological studies. 1-3 The striatum and hippocampus are particularly vulnerable to ischemic insult, and neuronal damage is expressed as an alteration of both intrinsic membrane properties and synaptic transmission of the recorded cells. 4 -6 A large body of experimental work has been devoted to explore the neuroprotective efficacy of drugs blocking glutamate neurotransmission in animal models of cerebral ischemia. 3,[7][8][9][10][11] More recently, however, attention has been also focused on ␥-aminobutyric acid (GABA) changes during ischemia and on possible neuroprotective effects of GABAergic drugs. [12][13][14][15] Although a number of studies have suggested that increasing GABAergic synaptic transmission might display neuroprotective effects against brain ischemia, 16 -20 the exact mechanisms underlying these effects have yet to be elucidated. Conclusions-AntiepilepticIncreasing GABA function might represent a beneficial therapeutic approach to acute ischemia for different reasons. 13,19,20 First, endogenous GABA synthesis and release with consequent reduction in GABAergic transmission are decreased after an ischemic insult. Second, since glutamatergic and GABAergic transmissions work by each counterbalancing the function of the other, enhancing GABAergic activity should balance excessive glutamatergic excitation, which is the pivotal event leading to cell death.The aim of the present study is to characterize the electrophysiological effects of 2 currently used GABAergic antiepileptic drugs, tiagabine and vigabatrin, and to examine the cellular sites at which they act by using recordings from rat cortico...

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Section: Discussionmentioning

confidence: 99%

Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia

Costa

Leone

Saulle

et al. 2004

Stroke

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“…19 In addition to metabolic effects, GABA may also elicit a potentially restorative local vasodilatory response. 20 Previous experimental work has correlated pharmacologically increased levels of GABA activity with lessened degree of neuronal ischemic injury in both brain [21][22][23][24] and spinal cord. 25 Other investigators, however, have not been able to demonstrate the benefit of GABAmimetic drugs in ischemia, particularly those agents relatively specific for the GABA-B receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Using a "functional assay" of outcome following ischemia (recovery from paraplegia), we demonstrated that pharmacologic activation of the GABA-A receptor improves outcome following ischemia, while pharmacologic inhibition of this receptor worsens outcome from this injury. 4 Vigabatrin has been shown to be protective in global ischemia models, 13,23 when given prior to ischemia. Topiramate has also shown suggestive benefit in global ischemia models.…”

Section: Discussionmentioning

confidence: 99%

Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid

Madden¹,

Clark²,

Lessov³

2003

Clinical Medicine & Research

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“…GABAergic agents, including tiagabine and vigabatrin (gamma-vinyl GABA), have been reported in preclinical studies to reduce the extent of ischemiamediated neuronal damage in vivo and in vitro (40,46,47), and thus it is not surprising that PLZ has been shown to reduce neuronal damage in an animal model of ischemia (8). It is also interesting to note that glutamate-associated excitotoxicity is also thought to play a role in the neurodegeneration observed in Alzheimer's disease (48)(49)(50) and GABAergic deficits have been reported in AD, although these latter findings are conflicting and complicated by variables such as illness severity and postmortem handling of brain tissue (51).…”

Section: Phenelzine Elevates Brain Gaba Levelsmentioning

confidence: 99%

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

MacKenzie

Song

Dursun

et al. 2010

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia

Cited by 88 publications

References 42 publications

Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia

Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia

Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

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Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia

Cited by 88 publications

References 42 publications

Coactivation of GABA A and GABA B Receptor Results in Neuroprotection During In Vitro Ischemia

Coactivation of GABA A and GABA B Receptor Results in Neuroprotection During In Vitro Ischemia

Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

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Product

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Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia

Coactivation of GABA _A and GABA _B Receptor Results in Neuroprotection During In Vitro Ischemia