[THE INFLUENCE OF SHORT-TIME CEREBRAL ISCHEMIA ON PIAL VESSELS ADRENOREACTIVITY IN RATS].

Reactivity of pial vessels in response to a brain surface irrigation by norepinephrine solution in rats, subjected to transient global cerebral ischemia (2VO+hypo model), was investigated. Four different groups of rats at 2, 7, 14 or 21 days after ischemia were subjected to microvascular studies using in vivo video microscopy method. The diameter changes of pial arteries and veins in response to norepinephrine were measured. It was established that cerebral ischemia led to increase the number of the constrictions to norepinephrine mainly at the vessels to relating to a group of small pial arteries and arterioles and pial veins of the 3rd generation. Reactivity changes were observed in all time points studied. These changes probably is connected with caused by ischemia the increase in reactivity and sensitivity of pial vessels adrenoceptors. The greatest changes are noted in 14 days after ischemia.

Intracerebroventricular administration of creatine protects against damage by global cerebral ischemia in rat.

Although a large body of evidence shows that pretreatment of brain tissue with creatine protects against anoxic injury in vitro, only a couple of papers have investigated creatine protection in vivo, and they yielded conflicting results. We attempted to clarify how creatine may be protective in an in vivo model of global cerebral ischemia (GCI). We administered creatine either before of after GCI. We decided to administer it by intracerebroventricular infusion, to maximize its bioavailability to the brain. Our findings show that creatine is clearly protective in vivo when administered before ischemia. In that case, histological evaluation of damage was consistently improved in all regions examined, and neurological score was better in creatine-treated rats than in controls. When administered after ischemia, histology was improved in the hippocampus, while only a not significant trend toward improvement was observed in the cerebral cortex and in the caudo-putamen. Neurological score was not improved by creatine administration after GCI. Our findings show that creatine administration is protective in vivo. Such protection was clear in the case of pretreatment, and was present, to a lesser degree, when treatment was started after ischemia. Our results should encourage further research in the possible role of creatine therapy in neuroprotection.

Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage.

Phosphocreatine can to some extent compensate for the lack of ATP synthesis that is caused in the brain by deprivation of oxygen or glucose. Treatment of in vitro rat hippocampal slices with creatine increases the neuronal store of phosphocreatine. In this way it increases the resistance of the tissue to anoxic or ischemic damage. In in vitro brain slices pretreatment with creatine delays anoxic depolarization (AD) and prevents the irreversible loss of evoked potentials that is caused by transient anoxia, although it seems so far not to be active against milder, not AD-mediated, damage. Although creatine crosses poorly the blood-brain barrier, its administration in vivo at high doses through the intracerebroventricular or the intraperitoneal way causes an increase of cerebral phosphocreatine that has been shown to be of therapeutic value in vitro. Accordingly, preliminary data show that creatine pretreatment decreases ischemic damage in vivo.