A Glycine Site Antagonist, ZD9379, Reduces Number of Spreading Depressions and Infarct Size in Rats With Permanent Middle Cerebral Artery Occlusion

Tatlısumak, Turgut; Takano, Kentaro; Meiler, Michael R.; Fisher, Marc

doi:10.1161/01.str.29.1.190

Cited by 38 publications

(14 citation statements)

References 35 publications

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“…Previous studies have shown that NMDA receptor antagonists depress the activation of spreading depression in vivo (Marrannes et al, 1988;Gill et al, 1992;McLachlan, 1992;Nellgard and Wieloch, 1992;Martin et al, 1994;Willette et al, 1994;Obrenovitch and Z ilkha, 1996;Tatlisumak et al, 1998). Our results point to a pivotal role for NMDA receptor activation in the initial onset of SD.…”

Section: Discussionsupporting

confidence: 67%

“…1 A). Previous reports (Marrannes et al, 1988;Gill et al, 1992;McLachlan, 1992;Nellgard and Wieloch, 1992;Martin et al, 1994;Willette et al, 1994;Obrenovitch and Zilkha, 1996;Tatlisumak et al, 1998) have demonstrated that spreading depression in vivo is delayed or inhibited by glutamate receptor antagonists. In hippocampal brain slices, application of the noncompetitive NMDA receptor antagonist MK-801 (50 M) inhibited the onset of spreading depression (Fig.…”

Section: Glutamate Is Involved In the Initial Phase Of Spreading Deprmentioning

confidence: 94%

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Glutamate Release through Volume-Activated Channels during Spreading Depression

1999

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Volume-sensitive organic anion channels (VSOACs) in astrocytes are activated by cell swelling and are permeable to organic anions, such as glutamate and taurine. We have examined the release of glutamate through VSOACs during the propagation of spreading depression (SD). SD was induced by bath application of ouabain in hippocampal brain slices and was monitored by imaging intrinsic optical signals, a technique that provides a measure of cellular swelling. The onset of SD was associated with increased light transmittance, confirming previous studies that cellular swelling occurs during SD. NMDA receptor antagonists, either noncompetitive (MK-801, 10-50 microM) or competitive (CGS-17355, 100 microM), reduced the rate of propagation of SD, indicating that glutamate release contributes to SD onset. SD still occurred in zero Ca(2+)-EGTA (0-Ca(2+)-EGTA) solution, a manipulation that depresses synaptic transmission. HPLC measurements indicated that, even in this solution, there was significant glutamate release. Two lines of experiments indicated that glutamate was released through VSOACs during SD. First, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a blocker of VSOACs, depressed the rate of propagation of SD in a manner similar to NMDA antagonists. Second, NPPB inhibited the release of glutamate during SD in 0-Ca(2+)-EGTA external solution. These results indicate that cellular swelling during SD causes the activation of VSOACs and the release of glutamate by permeation through this channel. Cellular swelling is a result of neuronal activity and is observed during excitotoxicity. Therefore, glutamate release from VSOAC activation could occur under conditions of cell swelling and contribute to excitotoxic damage.

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Section: Discussionsupporting

confidence: 67%

Section: Glutamate Is Involved In the Initial Phase Of Spreading Deprmentioning

confidence: 94%

Glutamate Release through Volume-Activated Channels during Spreading Depression

1999

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“…This relationship may be causal, because eliciting SpD remote from the infarct region [i.e., by potassium application (Busch et al, 1996;Takano et al, 1996) or electrical stimulation (Back et al, 1996)] results in larger infarct volumes. Accordingly, administration of drugs (Gill et al, 1992;Iijima et al, 1992;Mies et al, 1993Mies et al, , 1994Rawanduzy et al, 1997;Tatlisumak et al, 2000) or physiologic treatments (Chen et al, 1993) that decrease the frequency of SpD associated with ischemic injury is also neuroprotective.…”

Section: Introductionmentioning

confidence: 99%

Delayed Secondary Phase of Peri-Infarct Depolarizations after Focal Cerebral Ischemia: Relation to Infarct Growth and Neuroprotection

et al. 2003

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In focal cerebral ischemia, peri-infarct depolarizations (PIDs) cause an expansion of core-infarcted tissue into adjacent penumbral regions of reversible injury and have been shown to occur through 6 hr after injury. However, infarct maturation proceeds through 24 hr. Therefore, we studied PID occurrence through 72 hr after both transient and permanent middle cerebral artery occlusion (MCAo) via continuous DC recordings in nonanesthetized rats. PIDs occurred an average 13 times before reperfusion at 2 hr and then ceased for an average approximately 8 hr. After this quiescent period, PID activity re-emerged in a secondary phase, which reached peak incidence at 13 hr and consisted of a mean 52 PIDs over 2-24 hr. This phase corresponded to the period of infarct maturation; rates of infarct growth through 24 hr coincided with changes in PID frequency and peaked at 13 hr. In permanent MCAo, PIDs also occurred in a biphasic pattern with a mean of 78 events over 2-24 hr. Parameters of secondary phase PID incidence correlated with infarct volumes in transient and permanent ischemia models. The role of secondary phase PIDs in infarct development was further investigated in transient MCAo by treating rats with a high-affinity NMDA receptor antagonist at 8 hr after injury, which reduced post-treatment PID incidence by 57% and provided 37% neuroprotection. Topographic mapping with multielectrode recordings revealed multiple sources of PID initiation and patterns of propagation. These results suggest that PIDs contribute to the recruitment of penumbral tissue into the infarct core even after the restoration of blood flow and throughout the period of infarct maturation.

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“…Как свидетельствуют немногочисленные публикации по данной проблеме, практически единственным малоинвазивным методом исследования поляризационных процессов является регистрация УПП [13,17,18]. Альтерирующее действие деполяризации связывается с нарушением ионного гомеостаза, резким увеличением метаболической нагрузки при ишемии, что приводит к несоответствию между потребностью в энергетических субстратах и их поступлением в ткань [12,22]. Объем ишемического повреждения преимущественно связан с общим временем ишемической деполяризации [11].…”

Section: Discussionunclassified

Electrophysiological Disturbances at Spinal Cord Local Compression Injury

Шапкин¹,

Суфианова²,

Sufianov³

et al. 2009

Hir. pozvonoč.

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To study changes in the levels of direct potential (LDP) and electrospinogramm (ESG) at spinal cord local compressive injury. Material and Methods. The study was performed in 13 outbred male rats. A local compression spinal cord injury was modeled by graduated compression of the spinal cord at the T10 level during 15 minutes. Registration of bioelectric activity was carried out by Ag/AgCl electrodes by means of a 4-channel DC amplifier with 1 MOhm input resistance. Results. Simultaneous LDP and ESG registration is an effective method of spinal cord functional diagnostics. The isolated assessment of ESG or LDP changes has much less prognostic and diagnostic value; therefore complex registration of these parameters should be performed for more exact assessment of a spinal cord functional state. Conclusion. The suggested procedure for functional assessment of the spinal cord extends the possibilities of purposive search and study of new medicines for prophylaxis and treatment of patients with ischemic and traumatic lesions of the spinal cord.

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A Glycine Site Antagonist, ZD9379, Reduces Number of Spreading Depressions and Infarct Size in Rats With Permanent Middle Cerebral Artery Occlusion

Cited by 38 publications

References 35 publications

Glutamate Release through Volume-Activated Channels during Spreading Depression

Glutamate Release through Volume-Activated Channels during Spreading Depression

Delayed Secondary Phase of Peri-Infarct Depolarizations after Focal Cerebral Ischemia: Relation to Infarct Growth and Neuroprotection

Electrophysiological Disturbances at Spinal Cord Local Compression Injury

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