Changes in regional levels of putative neurotransmitter amino acids in brain under unilateral forebrain ischemia

Kolluri, V. R. Sastry; Lakshmi, Gaja

doi:10.1007/bf00964870

Cited by 18 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a first step to this aim, we examined a change in spontaneous excitatory transmission in the SG neurons of adult rat spinal cord slices following superfusion of an oxygen-and glucose-free medium (which simulates ischemia) by use of the conventional whole cell patch-clamp technique. Ischemia in the CNS results in the release of GABA (Sastry Kolluri and Lakshmi 1989;Phillis et al 1994) as well as L-glutamate. GABA released so may serve to rescue SG neurons from excitotoxicity owing to its inhibitory action (Nelson et al 2000), because SG neurons are innervated by not only Lglutamate-but also GABA-and/or glycine-containing interneurons in the spinal dorsal horn. Therefore we also examined whether or not GABA and glycine play a role in preventing neuronal death following ischemia.…”

Section: Introductionmentioning

confidence: 99%

GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat

Matsumoto

Kumamoto²,

Furue³

et al. 2003

Journal of Neurophysiology

View full text Add to dashboard Cite

An ischemia-induced change in glutamatergic transmission was investigated in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique; the ischemia was simulated by superfusing an oxygen- and glucose-free medium (ISM). Following ISM superfusion, 21 of 37 SG neurons tested produced an outward current (23 +/- 4 pA at a holding potential of -70 mV), which was followed by a slow and subsequent rapid inward current; the remaining neurons had only inward currents. During such a change in holding currents, spontaneous excitatory postsynaptic currents (EPSCs) were remarkably decreased in a frequency with time (half-decay time of the frequency: about 65 s). The frequency of spontaneous EPSCs was reduced to 28 +/- 13% (n = 37) of the control level during the generation of the slow inward current (about 4 min after the beginning of ISM superfusion) without a change in the amplitude of spontaneous EPSCs. When ISM was superfused together with either bicuculline (10 microM) or CGP35348 (20 microM; GABA(A) and GABA(B) receptor antagonists, respectively), spontaneous EPSC frequency reduced by ISM recovered to the control level and then the frequency markedly increased [by 325 +/- 120% (n = 22) and 326 +/- 91% (n = 17), respectively, 4 min after ISM superfusion]; this alteration in the frequency was not accompanied by a change in spontaneous EPSC amplitude. Superfusing TTX (1 microM)-containing ISM resulted in a similar recovery of spontaneous EPSC frequency and following increase (by 328 +/- 26%, n = 12) in the frequency; strychnine (1 microM) did not affect ISM-induced changes in spontaneous EPSC frequency (n = 5). It is concluded that the ischemic simulation inhibits excitatory transmission to SG neurons, whose action is in part mediated by the activation of presynaptic GABA(A) and GABA(B) receptors, probably due to GABA released from interneurons as a result of an ischemia-induced increase in neuronal activities. This action might protect SG neurons from an excessive excitation mediated by L-glutamate during ischemia.

show abstract

Section: Introductionmentioning

confidence: 99%

GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat

Matsumoto

Kumamoto²,

Furue³

et al. 2003

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…Although glutamate is an amino acid that is widely dis tributed throughout the entire CNS and its postsynaptic receptors are found in virtually all neurons [1], it is found at higher concentrations in neurons of the cerebral cortex and hippocampus [12]. In the hum an we have recently demonstrated an elevation in glutamate levels in acute cerebral ischemia, and its relationship to lesion size, neu rological deficit [l 1], and early neurological deterioration [13], In this study we examined glutamate levels with respect to infarct topography.…”

Section: Introductionmentioning

confidence: 99%

Glutamate Is a Marker for Cerebral Ischemia in Cortical but Not Deep Infarcts

Castillo¹,

Dávalos²,

Lema³

et al. 1997

Cerebrovasc Dis

View full text Add to dashboard Cite

We analyzed glutamate levels in cerebrospinal fluid (CSF) with respect to cerebral infarct topography in 67 patients with cortical infarcts and 78 with deep infarcts of less than 24 h duration. Infarct volume and topography were determined on repeated cerebral CT performed between 4 and 7 days after admission. Stroke severity was evaluated by the Canadian Stroke Scale (CSS) at 48 h after inclusion. Glutamate concentration in CSF was 8.4 ± 4.9 µmol/l in patients with cortical infarcts and 6.5 ± 5.2 µmol/l in patients with deep infarcts (p = 0.028). In cortical infarcts, glutamate levels correlated with the CSS score (Spearman coefficient –0.601, p < 0.001) and with the infarct volume (Spearman coefficient 0.671, p < 0.001). In the logistic regression analysis, glutamate was an independent predictor for stroke severity (high: CSS score < 5; low: CSS score ≧ 5) after controlling for age, inclusion delay, body temperature, glucose levels and fibrinogen (odds ratio = 1.3; 95% confidence interval= 1.07–1.67). Glutamate was not related significantly with the severity and size of deep cerebral infarcts. Early neurological deterioration was more frequent in cortical infarcts than in deep infarcts (43 vs. 19%, p < 0.001), and was independently related to glutamate levels in CSF. These results suggest that drugs that inhibit or antagonize glutamate may be useful particularly in cortical infarcts.

show abstract

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Inglefield¹,

Perry²,

Schwartz³

1995

Hippocampus

View full text Add to dashboard Cite

The neuroprotective effects of enhancing neuronal inhibition with a gamma-aminobutyric acid (GABA) uptake inhibitor were studied in gerbil hippocampus following transient ischemia. We used in vivo microdialysis to determine a suitable dosing regimen for tiagabine (NNC328) to elevate extracellular levels of GABA within the hippocampus. In anesthetized (normothermic) gerbils, tiagabine (45 mg/kg, i.p.) selectively elevated extracellular GABA levels 450% in area CA1 of the hippocampus. In gerbils subjected to cerebral ischemia via 5-min bilateral carotid occlusion, extracellular GABA levels increased 13-fold in area CA 1 returning to baseline within 30-45 min. When tiagabine was injected 10 min following onset of reperfusion, GABA levels remained elevated (200-470%) for 90 min. In addition, tiagabine significantly reduced the ischemic-induced elevation of glutamate levels in area CA1 during the postischemic period when GABA levels were elevated. There was no effect of postischemic tiagabine on aspartate or six other amino acids. Using the same dosing regimen, we evaluated the degree of neuroprotection in the hippocampus of gerbils 4 and 21 days after ischemia. Tiagabine decreased body temperature a maximum of 2.7 degrees C beginning 30 min into reperfusion and lasting 90 min. In untreated gerbils sacrificed 4 and 21 days after ischemia, there was severe necrosis (99%) of the pyramidal cell layer in area CA1. Whereas tiagabine significantly protected the CA1 pyramidal cell layer in ischemic gerbils at 4 days (overt necrosis confined to about 17% of area CA1), the protection diminished significantly 21 days postischemia. When normothermia was maintained both during and after ischemia in a separate group of tiagabine-treated animals, approximately 77% of the CA1 pyramidal cell layer was necrotic at 4 days. Based on these findings, we suggest that 1) tiagabine slows the development of hippocampal degeneration following ischemia, and 2) that mild, postischemic hypothermia is responsible, in large part, for the neuroprotective actions of this drug. We conclude that the histological outcome after administration of cerebral neuroprotectants should be assessed following long-term survival.

show abstract

Changes in regional levels of putative neurotransmitter amino acids in brain under unilateral forebrain ischemia

Cited by 18 publications

References 18 publications

GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat

GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat

Glutamate Is a Marker for Cerebral Ischemia in Cortical but Not Deep Infarcts

Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus

Contact Info

Product

Resources

About