ryanodine and Ischemic-Attack--Transient

Ryanodine receptors located on the sarcoplasmic or endoplasmic reticulum, play an important role in the regulation of the intracellular Ca2+ level via the mechanism of Ca(2+)-induced Ca2+ release (CICR). Perturbation of intracellular Ca2+ regulation has been considered to be one of the most important mechanisms underlying acute ischemic neuronal damage. The ryanodine binding, an indicator of intracellular channels of CICR, and local cerebral blood flow (LCBF) were therefore examined at 15 min post-ischemia in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to determine both parameters within the same brain. Severe hemispheric cerebral ischemia was induced by occluding the right common carotid artery. LCBF was measured at the end of the experiment using [14C]iodoantipyrine method. The ryanodine binding was evaluated autoradiographically in vitro using [3H] ryanodine. A group of gerbils who underwent a sham procedure served as controls. LCBF was found to be significantly decreased in most cerebral regions on the occluded side. In contrast, a significant reduction in ryanodine binding was noted only in the hippocampus CA1 on the occluded side. Taken together, these findings indicate that the CICR in the hippocampus CA1 may be especially susceptible to acute ischemic stress, and be closely associated with the pathophysiological mechanisms of the selective vulnerability of this region.

Topics: Animals; Gerbillinae; Hippocampus; Ischemic Attack, Transient; Male; Ryanodine; Time Factors

Alterations in ryanodine binding and local cerebral blood flow (LCBF) were examined at 30 minutes and 2 hours post-ischemia in the gerbil brain in order to evaluate the influence of cerebral ischemia on the intracellular channels of Ca2+-induced Ca2+ release (CICR). Severe hemispheric cerebral ischemia was induced by occluding the right common carotid artery. LCBF was measured at the end of the experiment using [14C]iodoantipyrine method, and the ryanodine binding was evaluated in vitro using [3H]ryanodine as a specific ligand for CICR channels. An autoradiographic method developed in our laboratory enabled us to determine both parameters within the same brain. A group of gerbils who underwent a sham procedure served as controls. LCBF was found to be significantly reduced in most of the cerebral regions on the occluded side at both 30 minutes as well as 2 hours post-ischemia. In contrast, a significant reduction in ryanodine binding was noted only in the hippocampus CA1 on the occluded side at 30 minutes and 2 hours after the occlusion. These findings suggest that regionally specific changes of CICR may be the cause of decreased ryanodine binding in the hippocampus CA1, and that these changes may be related to the pathophysiological mechanisms that cause this region to be particularly vulnerable to ischemia.

Topics: Animals; Antipyrine; Autoradiography; Brain; Calcium; Calcium Channels; Carbon Radioisotopes; Gerbillinae; Hippocampus; Ischemic Attack, Transient; Male; Muscle Proteins; Pyramidal Cells; Radioligand Assay; Regional Blood Flow; Reperfusion; Ryanodine; Ryanodine Receptor Calcium Release Channel; Tritium

The effect was examined of dantrolene, a drug for malignant hyperthermia acting through preventing release of Ca from the ryanodine-type intracellular stores in muscle cells, on ischemic delayed neuronal death in field CA1 of gerbil hippocampus. Dantrolene (1.6 mM in concentration, 3 microliters each in volume), when administered bilaterally in the lateral ventricles 30 min after reperfusion after transient forebrain ischemia for 3 min at 37 degrees C, significantly protected against the neuronal death. It is proposed that the dantrolene-sensitive (most likely, the ryanodine-type) intracellular Ca stores in CA1 pyramidal cells play a pivotal role in the development of ischemic neuronal damage.

Topics: Animals; Brain; Carotid Arteries; Cell Death; Dantrolene; Gerbillinae; Hippocampus; Injections, Intraventricular; Ischemic Attack, Transient; Male; Neurons; Pyramidal Cells; Ryanodine