Mechanisms Of Ischemic Brain Damage Research Articles

Blockade of nitric oxide formation by [formula omitted] mitigates ischemic brain edema and subsequent cerebral infarction in rats

In order to investigate whether or not nitric oxide (NO) formation underlies the cellular mechanisms of ischemic brain damage, we examined the effects of Nω-nitro-l-arginine (l-NNA), a NO synthase inhibitor, on ischemic brain edema and subsequent infarction in rats with middle cerebral artery occlusion (MCAo). For this purpose, administrations of l-NNA (1 mg/kg, i.p.) to each animal were done at the time of 5 min, 3, 6 and 24 h after MCAo, respectively. It was shown from this study that l-NNA significantly mitigated ischemic cerebral edema, and histological examinations revealed that this compound markedly reduced infarction size that occurred following MCAo. These results strongly suggest that NO formation is at least partly involved in the pathogenetic mechanisms of ischemic brain edema and subsequent cerebral infarction.

Postischemic alteration of muscarinic acetylcholine and adenosine A1 binding sites in gerbil brain

We studied the alterations in the binding of muscarinic cholinergic and adenosine A1 receptors following transient cerebral ischemia in Mongolian gerbils and examined the effects of the novel vinca alkaloid derivative vinconate and pentobarbital against the alterations in the binding of these receptors. Animals were allowed to survive for 5 h and 7 days after 10 min of cerebral ischemia induced by bilateral occlusion of common carotid arteries. [3H]Quinuclidinyl benzilate (QNB) and [3H]cyclohexyladenosine (CHA) were used to label muscarinic cholinergic and adenosine A1 receptors, respectively. The [3H]QNB and [3H]CHA bindings showed no significant alteration in the gerbil brain 5 h after ischemia. However, these bindings in the striatum, the hippocampal CA1 sector, and the hippocampal CA3 sector revealed a significant reduction 7 days after ischemia. The [3H]CHA binding also showed a significant decline in the dentate molecular layer 7 days after ischemia. Intraperitoneal application of vinconate (100 and 300 mg/kg) 10 min and pentobarbital (40 mg/kg) 30 min before ischemia showed a mild reduction in the [3H]CHA binding in the brain 5 h after ischemia. Especially, the reduction was found in the hippocampal CA1 sector and the dentate molecular layer. However, the [3H]QNB binding revealed no significant alteration in the brain 5 h after ischemia. Seven days after ischemia, both drugs prevented a marked reduction in the [3H]CHA binding in the striatum, but not in the hippocampal CA1 sector, the hippocampal CA3 sector, and the dentate molecular layer. By contrast, vinconate and pentobarbital failed to prevent the reduction in the [3H]QNB binding in the striatum. Morphological study indicated that vinconate and pentobarbital ameliorated the neuronal damage to the striatum, but not the hippocampal damage 7 days after ischemia. This histological finding was relatively consistent with the alteration in the [3H]CHA binding. These receptor autoradiographic and histological data suggest that vinconate and pentobarbital can protect the brain from both cellular and functional consequences of ischemia. These findings are of interest in relation to the mechanisms of ischemic brain damage.

Autoradiographic analysis of dopamine D 1 receptors in the gerbil brain following transient cerebral ischemia

1. 1. We studied the postischemic time-course of dopamine D 1 receptors in selectively vulnerable areas in the gerbil using receptor autoradiography. 2. 2. [ 3H]SCH 23390 was used to label dopamine D 1 receptors and transient cerebral ischemia was induced for 10 min. 3. 3. [ 3H]SCH 23390 binding showed no significant alteration in selectively vulnerable areas at an early stage (1–24 hr) of recirculation. Thereafter, [ 3H]SCH 23390 binding showed a significant reduction in most selectively vulnerable areas 48 hr or 7 days of recirculation. The ventromedial striatum and dentate gyrus which were resistant to ischemia also exhibited a significant reduction in [ 3H]SCH 23390 binding. 4. 4. Especially, marked reduction was noted in the dorsolateral striatum. However, this reduction in the dorsolateral striatum was not seen early in the recirculation prior to morphological neuronal damage. 5. 5. The result suggests that transient cerebral ischemia can cause a severe reduction in dopamine D 1 receptors in most selectively vulnerable areas. Furthermore, they suggest that dopamine D 1 transmission is not always responsible for the evolution of ischemic brain damage. 6. 6. These findings are discussed in relation to the mechanism of ischemic brain damage.

Evidence against major compartmentalization of H+ in ischemic rat brain tissue.

Ischemia leads to intracellular acidosis, the severity of which depends on the availability of glucose for production of lactate and H+. It has been suggested that major compartmentalization of H+ occurs, with glial cells becoming much more acidotic than neurons. Since this issue is of crucial importance for the understanding of mechanisms of ischemic brain damage, we induced complete ischemia by decapitation in hypo-, normo- and hyperglycemic awake rats, yielding brain tissue lactate contents varying between 4 and 27 mumol/g. Using phosphorus nuclear magnetic resonance (NMR) we explored whether a splitting of the phosphorus peak occurred as a reflection of compartmentalization. Forebrains were put in NMR tubes and spectra obtained 15 min after decapitation. Since no such splitting was observed, we conclude that major compartmentalization does not occur in ischemia at the degrees of lactic acidosis studied.