scholarly journals Gabapentin reduces infarct volume but does not suppress peri-infarct depolarizations

2011 ◽  
Vol 31 (7) ◽  
pp. 1578-1582 ◽  
Author(s):  
Ulrike Hoffmann ◽  
Jeong Hyun Lee ◽  
Tao Qin ◽  
Katharina Eikermann-Haerter ◽  
Cenk Ayata
Keyword(s):  
Blood Flow ◽  
Brain Injury ◽  
Spreading Depression ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Focal Ischemia ◽  
Stroke Outcome ◽  
Depolarization Wave ◽  
Transient Focal Ischemia

Spreading depression (SD) is an intense depolarization wave implicated in brain injury. In focal ischemia, recurrent peri-infarct depolarization (PID) waves akin to SD worsen the ischemic injury by exacerbating the blood flow-metabolism mismatch. We recently showed that gabapentin suppresses SD. We, therefore, tested gabapentin on PIDs and stroke outcome. Gabapentin pretreatment (200 mg/kg, intravenously) reduced the infarct volume by 23% after transient focal ischemia in mice. However, the frequency and duration of PIDs were not suppressed when recorded for 2hours during ischemia, suggesting that gabapentin reduces infarct volume independent of PID suppression.

Aggravation of brain injury after transient focal ischemia in p53-deficient mice

2001 ◽  
Vol 88 (1-2) ◽  
pp. 54-61 ◽  
Author(s):  
Keiichiro Maeda ◽  
Ryuji Hata ◽  
Frank Gillardon ◽  
Konstantin-Alexander Hossmann
Keyword(s):  
Brain Injury ◽  
Focal Ischemia ◽  
Transient Focal Ischemia ◽  
Deficient Mice

scholarly journals Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

2010 ◽  
Vol 31 (4) ◽  
pp. 1107-1118 ◽  
Author(s):  
Slavianka G Moyanova ◽  
Federica Mastroiacovo ◽  
Lidia V Kortenska ◽  
Rumiana G Mitreva ◽  
Erminia Fardone ◽  
...  
Keyword(s):  
Brain Damage ◽  
Metabotropic Glutamate Receptors ◽  
Infarct Volume ◽  
Focal Ischemia ◽  
Protective Role ◽  
Ischemic Brain Damage ◽  
Systemic Injection ◽  
Ischemic Brain ◽  
Metabotropic Glutamate ◽  
Transient Focal Ischemia

We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10 mg/kg, subcutaneous, administered once 30 minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%. The drug was inactive in mGlu4 receptor knockout mice. In the Et-1 model, PHCCC administered only once 20 minutes after ischemia reduced the infarct volume to a larger extent in the caudate/putamen than in the cerebral cortex. Ischemic rats treated with PHCCC showed a faster recovery of neuronal function, as shown by electrocorticographic recording and by a battery of specific tests, which assess sensorimotor deficits. These data indicate that activation of mGlu4 receptors limit the development of brain damage after permanent or transient focal ischemia. These findings are promising because selective mGlu4 receptor enhancers are under clinical development for the treatment of Parkinson's disease and other central nervous system disorders.

PPBP [4-Phenyl-1-(4-phenylbutyl) Piperidine] Decreases Brain Injury After Transient Focal Ischemia in Rats

Stroke ◽  
1996 ◽  
Vol 27 (11) ◽  
pp. 2120-2123 ◽  
Author(s):  
Hiroshi Takahashi ◽  
Jeffrey R. Kirsch ◽  
Kenji Hashimoto ◽  
Edythe D. London ◽  
Raymond C. Koehler ◽  
...  
Keyword(s):  
Brain Injury ◽  
Focal Ischemia ◽  
Transient Focal Ischemia

Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia

2004 ◽  
Vol 363 (3) ◽  
pp. 218-223 ◽  
Author(s):  
Yumin Luo ◽  
Zhen Qin ◽  
Zhen Hong ◽  
Xinmin Zhang ◽  
Ding Ding ◽  
...  
Keyword(s):  
Brain Injury ◽  
Murine Model ◽  
Focal Ischemia ◽  
Ischemic Brain Injury ◽  
Astragaloside Iv ◽  
Ischemic Brain ◽  
Transient Focal Ischemia

scholarly journals Late Reversal of Cerebral Perfusion and Water Diffusion after Transient Focal Ischemia in Rats

2002 ◽  
Vol 22 (3) ◽  
pp. 253-261 ◽  
Author(s):  
Lei Wang ◽  
Victor E. Yushmanov ◽  
Serguei M. Liachenko ◽  
Pei Tang ◽  
Ronald L. Hamilton ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Focal Ischemia ◽  
Artery Occlusion ◽  
Tissue Water ◽  
Apparent Diffusion ◽  
Reperfusion Period ◽  
Adc Values ◽  
Transient Focal Ischemia ◽  
Late Reperfusion

Region-specific cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) of tissue water in the rat brain were quantified by high-field magnetic resonance imaging at 9.4 T in the rat suture occlusion model. Cerebral blood flow and ADC were compared during the short- (4.5 hours) and long-term (up to 6 days) reperfusion after 80 minutes of transient middle cerebral artery occlusion, and correlated with the histology analysis. On occlusion, average CBF fell from ∼100 to less than 50 mL 100 g−1 min−1 in the cortex, and to less than 20 mL 100 g−1 min−1 in the caudate putamen (CP). Corresponding ADC values decreased from (6.98 ± 0.82) × 10−4 to (5.49 ± 0.54) × 10−4 mm2/s in the cortex, and from (7.16 ± 0.58) × 10−4 to (4.86 ± 0.62) × 10−4 mm2/s in the CP. On average, CBF recovered to ∼50% of baseline in the first 24 hours of reperfusion. After 2 to 4 days, a strong hyperperfusion in the ipsilateral cortex and CP, up to ∼300 mL 100 g−1 min−1, was observed. The ADC ratio in the ipsilateral and contralateral CP was also inverted in the late reperfusion period. Histology revealed more severe tissue damage at the late stage of reperfusion than at 4.5 hours. Significant reversal of CBF and ADC during the late reperfusion period may reflect the impairment of autoregulation in the ischemic regions. Vascular factors may play an important role in the infarct development after 80-minute focal ischemia.

scholarly journals Modulation by Nitric Oxide of Cerebral Neutrophil Accumulation after Transient Focal Ischemia in Rats

2000 ◽  
Vol 20 (5) ◽  
pp. 812-819 ◽  
Author(s):  
Sophie Batteur-Parmentier ◽  
Isabelle Margaill ◽  
Michel Plotkine
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Focal Ischemia ◽  
Left Middle Cerebral Artery ◽  
No Production ◽  
Myeloperoxidase Activity ◽  
Transient Focal Ischemia

A beneficial role of nitric oxide (NO) after cerebral ischemia has been previously attributed to its vascular effects. Recent data indicate a regulatory role for NO in initial leukocyte-endothelial interactions in the cerebral microcirculation under basal and ischemic conditions. In this study, the authors tested the hypothesis that endogenous NO production during and/or after transient focal cerebral ischemia can also be neuroprotective by limiting the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left middle cerebral artery and the left common carotid artery. The effect of NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, intraperitoneally), an NO synthase inhibitor, was examined at 48 hours after ischemia on both infarct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical infarct volume by 34% and increased cortical myeloperoxidase activity by 60%, whereas administration of L-NAME at 1, 7, and 22 hours of reperfusion had no effect. Such exacerbations of infarction and myeloperoxidase activity produced when L-NAME was given 5 minutes after the onset of ischemia were not observed in rats rendered neutropenic by vinblastine. These results suggest that after transient focal ischemia, early NO production exerts a neuroprotective effect by modulating neutrophil infiltration.

Characteristics of induced spreading depression after transient focal ischemia in the rat

2000 ◽  
Vol 861 (2) ◽  
pp. 316-324 ◽  
Author(s):  
Katsuyoshi Shimizu ◽  
Roland Veltkamp ◽  
David W. Busija
Keyword(s):  
Spreading Depression ◽  
Focal Ischemia ◽  
Transient Focal Ischemia

scholarly journals Fastigial Stimulation Increases Ischemic Blood Flow and Reduces Brain Damage after Focal Ischemia

1993 ◽  
Vol 13 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
Fangyi Zhang ◽  
Costantino Iadecola
Keyword(s):  
Blood Flow ◽  
Brain Damage ◽  
Infarct Volume ◽  
Group Analysis ◽  
Blood Gases ◽  
Focal Ischemia ◽  
Ischemic Damage ◽  
Collateral Flow ◽  
Sprague Dawley ◽  
Mca Occlusion

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation “protects” the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague–Dawley rats were anesthetized (halothane 1–3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 μA; 50 Hz; 1 s on–1 s off) while AP was maintained at 97 ± 11 mm Hg (mean ± SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thioninstained sections. In unstimulated rats ( n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion ( n = 12) enhanced CBF and EEG recovery [61 ± 34 and 73 ± 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (Pco2 = 64 ± 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05). Thus, FN stimulation, unlike hypercapnia, increases CBF to the ischemic cortex, improves recovery of electrical activity, and reduces tissue damage after MCA occlusion. These findings support the hypothesis that FN stimulation reduces ischemic damage by enhancing collateral flow to the ischemic territory.

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