Background and Purpose-Purinergic nucleoside inosine elicits protection and regeneration during various injuries. The purpose of this study was to examine the protective effects of inosine against cerebral ischemia. Methods-Adult Sprague-Dawley rats were anesthetized. Inosine, hypoxathine, or vehicle was administered intracerebroventricularly before transient right middle cerebral artery occlusion (MCAo). Animals were placed in behavioral chambers 2 days to 2 weeks after MCAo and then euthanized for tri-phenyl-tetrazolium chloride staining. Glutamate release was measured by microdialysis/high-performance liquid chromatography, and single-unit action potentials were recorded from neurons in the parietal cortex. Results-Stroke animals receiving inosine pretreatment demonstrated a higher level of locomotor activity and less cerebral infarction. Intracerebroventricular administration of the same dose of hypoxanthine did not confer protection. Coadministration of selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(Ϯ)-dihydropyridine-3,5-dicarboxylate (MRS1191) significantly reduced inosine-mediated protection. Inosine did not alter basal glutamate release, nor did it reduce ischemia-evoked glutamate overflow from cerebral cortex. However, inosine antagonized glutamate-induced electrophysiological excitation in cerebral cortical neurons. Key Words: inosine, adenosine Ⅲ neuroprotection Ⅲ stroke T he purinergic nucleoside inosine elicits protection and regeneration during various injuries. Inosine reduced zinc-induced injury in PC12 cells, 1 reduced toxicity after oxygen-glucose deprivation (OGD) in rat astrocyte cultures, 2 and preserved cell viability during chemical hypoxia induced by rotenone in spinal cord cell culture. 3 The protective effect of inosine has also been demonstrated in vivo. Infusion of inosine reduced ischemic/hypoxic injury in myocardium. 4 The roles of inosine in central nervous system (CNS) during ischemia have not been studied extensively. Middle cerebral artery occlusion (MCAo) led to release of inosine and its metabolite hypoxanthine from the ischemic cortex in stroke animals. 5 Inosine, given after stroke, stimulated axonal outgrowth and improved behavioral outcome in stroke animals. 6 These data suggest that inosine promotes neuroregeneration after stroke. It is still not clear whether inosine, given before cerebral ischemia, is neuroprotective. Conclusions-InosineSeveral protective mechanisms of inosine have been proposed from in vitro studies. Inosine binds selectively to A3, but not A1 or A2A, receptors in human embryonic kidney (HEK)-293 cells. Exogenous application of inosine increased ATP level in PC12 cells. Such an effect was not found with selective A1, A2A, or A3 agonists, indicating that the inosine-induced elevation of ATP levels did not relate to these purinergic receptors in PC12 cells. 7 Inosine or its analog inosine 5Ј-triphosphate reduced glutamate receptor-mediated responses in hippocampal CA1 synapse 8 or N-methyl-Daspartate-mediated n...

Supraorbital keyhole surgery is a limited surgical procedure with reduced traumatic manipulation of tissue and entailing little time in the opening and closing of wounds. We utilized the approach to treat head injury patients complicated with optic nerve compression and cerebrospinal fluid leakage (CSF). Eleven cases of basal skull fracture complicated with either optic nerve compression and/or CSF leakage were surgically treated at our department from February 1995 to June 1999. Six cases had primary optic nerve compression, four had CSF leakage and one case involved both injuries. Supraorbital craniotomy was carried out using a keyhole-sized burr hole plus a small craniotomy. The size of craniotomy approximated 2 x 3 cm2. The optic nerve was decompressed via removal of the optic canal roof and anterior clinoid process with high-speed drills. The defect of dura was repaired with two pieces of tensa fascia lata that were attached on both sides of the torn dural defect with tissue glue. Seven cases with optic nerve injury included five cases of total blindness and two cases of light perception before operation. Vision improved in four cases. The CSF leakage was stopped successfully in all four cases without complication. As optic nerve compression and CSF leakage are skull base lesions, the supraorbital keyhole surgery constitutes a suitable approach. The supraorbital keyhole surgery allows for an anterior approach to the skull base. This approach also allows the treatment of both CSF leakage and optic nerve compression. Our results indicate that supraorbital keyhole operation is a safe and effective method for preserving or improving vision and attenuating CSF leakage following injury.

Dopamine (DA), a major neurotransmitter used in the striatum, is involved in movement disorders such as Parkinson's disease and Huntington's chorea. With the loss of neurons in the striatum of patients with Huntington's disease (HD), there is an associated downregulation of DA receptors, which may alter DA-mediated responses. In the present study, DA-mediated electrophysiological depression was studied in animals with quinolinic acid (QA)-induced experimental HD. QA was directly applied to the right striatum of adult female Sprague-Dawley rats. Animals receiving QA developed ipsilateral rotation after the application of apomorphine. Fetal striatal tissue transplants grafted 1 month after lesioning attenuated apomorphine-induced rotation. Six months after lesioning, the animals were anesthetized with urethane for electrophysiological study. DA, applied directly to neurons by pressure microejection, inhibited spontaneous single-unit activity in the striatal neurons of nonlesioned, lesioned and lesioned/grafted rats. QA lesioning reduced responses to DA in the striatal neurons. The dose of DA required to inhibit striatal neuron activity in the lesioned rats was significantly increased compared to that in the nonlesioned rats. Transplantation of fetal striatal tissue restored the electrophysiological sensitivity to DA in the lesioned striatum. The dose of DA used to suppress striatal neuron activity was reduced after grafting. Immunohistostaining showed survival of gamma-aminobutyric acid neurons at the graft site. Tyrosine hydroxylase-positive terminals were found innervating the striatal grafts. In conclusion, our data demonstrate that fetal striatal transplants restore electrophysiological sensitivity to DA in the lesioned striatum of animals with experimental HD.