We examined the change of regional cerebral blood flow (rCBF) and local cerebral glucose utilization (LCGU) in the middle cerebral artery (MCA) occlusion or recirculation model of rats, and tested anti-ischemic effects of a free radical scavenger, 3-methyl-1-phenyl-pyrazolon-5-one (MCI-186). A remarkable increase in LCGU was observed in the cortex supplied by the anterior cerebral artery after recirculation. This hypermetabolism of glucose was at least partly caused by the postischemic oxidative injury, since MCI-186 ameliorated the high LCGU in this area. These results suggested the usefulness of this type of free radical scavenger for inhibiting the postischemic injury.

Animals↗

PubMedDate not supplied

The mechanism of ischemia-induced brain cell injury. The membrane theory.

Temporal ischemia of the brain injures only the selectively vulnerable brain cells. The dying process evolves along with glutamate-mediated intracellular signal-transduction system, together with a loss of Ca2+ homeostasis. Such post-ischemic changes eventually disrupt functional and structural integrity of the cell membrane and kill the neuron. Molecular basis in pharmacoprotective agents is discussed.

Animals↗

PubMedDate not supplied

Preserved neurotransmitter receptor binding following ischemia in preconditioned gerbil brain.

Preconditioning the brain with sublethal ischemia induces tolerance to subsequent ischemic insult. Using [3H]quinuclidinyl benzilate (QNB), [3H]MK 801, [3H]cyclohexyladenosine, [3H]muscimol, and [3H]PN200-110, we investigated the alterations in neurotransmitter receptor and calcium channel binding in the gerbil hippocampus following ischemia with or without preconditioning. Two-minute forebrain ischemia, which produced no neuronal damage, resulted in no alterations in binding except for a slight reduction in [3H]QNB binding in the CA1 subfield. Three-minute ischemia destroyed the majority of CA1 pyramidal cells and caused, in CA1, reductions in binding of all ligands used. Preconditioning with 2-min ischemia followed by 4 days of reperfusion protected against CA1 neuronal damage and prevented the reductions in binding although [3H]QNB and [3H]PN200-110 binding transiently decreased in the early reperfusion period, suggesting down-regulation. Thus, preconditioning protects against damage to the neurotransmission system as well as histopathological neuronal death.

Adenosine↗

PubMedDate not supplied

Calcium entry blocker ameliorates ischemic neuronal damage in monkey hippocampus.

Effects of treatment with (+/-)-1-(3,4-dimethoxyphenyl)-2-(4- diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100), a calcium entry blocker, on ischemic neuronal damage were investigated. Monkeys were subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral arteries) major arteries. Blood flow was restored after 5, 10, 13, and 15 min occlusion, and NC-1100 (1 mg/kg) was then immediately infused intravenously. Monkeys were killed by perfusion fixation 5 days after occlusion. All brain regions were then histologically investigated for ischemic neuronal changes. Physiological data of NC-1100-treated subjects were not significantly different than those of untreated subjects. Heart rate tended to decrease after ischemia in treated subjects. Occlusion of 8 arteries for 10 to 15 min produced ischemic neuronal damage confined exclusively to the CA1 subfield of the hippocampus. Treatment with NC-1100 markedly reduced ischemic neuronal damage in the CA1 subfield of the hippocampus. It is suggested that postischemic treatment with the calcium entry blocker, NC-1100, might protect the brain from the ischemic damage produced in patients suffering from transient ischemia.

Animals↗

PubMedDate not supplied

Effects of 50 ppm NO2 gas exposure on physiological functions of rats.

When rats were exposed to 50 ppm NO2 gas for 36 h, remarkable changes in some biochemical levels compared with those of control rats were observed. Namely, levels of total cholesterol, ester cholesterol, total lipids, triglycerides, nitrogen of urea, uric acid, glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and cytochrome P-450 of the exposed rats were decidedly different from those of the control rats. Thus, it was suggested that functions of liver are acutely injured upon exposure to 50 ppm NO2 gas, although extensive pulmonary injury resulting from such an exposure may also be responsible for some of the abnormal serum values.

Alanine Transaminase↗