thiourea and Cerebral-Hemorrhage

Although intracerebral hemorrhage (ICH) increases the level of glutamate in the perihematomal area and cerebral spinal fluid (CSF) in the ICH acute phase, it is unclear whether elevated glutamate activates neuronal nitric oxide synthase (nNOS) in the ICH brain and whether nNOS is an important target for ICH treatment. Here, we assessed the role of the nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) in the activity of NADPH-d and ICH-induced brain injuries. An autologous blood intracerebral infusion model in male rats was used. All of the rats were sacrificed 24h after ICH. ICH increased NADPH-d activity in the striatum. Administering SMTC 3h after ICH decreased the activity of NADH-d (p<0.05 vs. the ICH group). The activation of gelatinolytic enzymes in the perihematomal region of the striatum was reduced by SMTC treatment (p<0.01, vs. the ICH group). The loss of laminin- and occludin-stained vessels was significant in perihematomal regions after 24h of ICH and was significantly attenuated by the administration of SMTC (p<0.01 for laminin, p<0.05 for occluding, compared with the ICH group). Neuronal death and neurological deficits after ICH were also decreased in SMTC treatment rats (p<0.01, vs. the ICH group). The results suggest that the administration of the nNOS inhibitor SMTC after ICH protects against ICH-induced brain injuries and improves neurological function.

Topics: Animals; Brain; Cell Death; Cerebral Hemorrhage; Citrulline; Corpus Striatum; Disease Models, Animal; Enzyme Inhibitors; Laminin; Male; Microvessels; Motor Activity; NADPH Dehydrogenase; Neurons; Neuroprotective Agents; Nitric Oxide Synthase; Occludin; Posture; Rats, Sprague-Dawley; Thiourea

Iron compounds formed in the degradation of a hematoma can accelerate the formation of free radicals in adjacent ischemic or hypoperfused tissue. The purpose of this study was to examine the efficacy of compounds that quench free radicals in improving the outcome in rats with experimental intracerebral hemorrhage. Intracerebral hemorrhage was induced in rats by injection of bacterial collagenase and heparin into the caudate nucleus. Rats were treated with alpha-tocopherol plus ascorbic acid starting before hemorrhage, or with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone starting 2 h after hemorrhage, with treatment continued for 10 days after induction of hemorrhage. Outcome was assessed by behavioral analyses, magnetic resonance imaging, and histopathology. A trend towards behavioral improvement was found for rats treated with alpha-tocopherol/ascorbic acid, while behavior was significantly improved following intracerebral hemorrhage in rats treated with dimethylthiourea or alpha-phenyl-N-tert-butyl nitrone. These results suggest that free radicals may play a role in the development of brain injury following intracerebral hemorrhage, and that compounds that interrupt the free radical cascade may improve outcome. However, treatment did not significantly affect edema, resolution of the hematoma, or neuronal injury in tissue adjacent to the hemorrhage.

Topics: Animals; Ascorbic Acid; Behavior, Animal; Body Temperature; Cerebral Hemorrhage; Cyclic N-Oxides; Feeding Behavior; Free Radical Scavengers; Free Radicals; Magnetic Resonance Imaging; Male; Neurologic Examination; Neuroprotective Agents; Nitrogen Oxides; Rats; Rats, Sprague-Dawley; Thiourea; Vitamin E

Topics: Anatomy; Anesthesia; Anesthesia, Inhalation; Anesthesia, Local; Autoradiography; Barbiturates; Blood-Brain Barrier; Body Temperature; Brain; Brain Diseases; Brain Injuries; Brain Neoplasms; Carbon Isotopes; Central Nervous System; Cerebral Hemorrhage; Embryology; Humans; Infections; Intracranial Embolism and Thrombosis; Models, Biological; Muscles; Permeability; Regional Blood Flow; Sulfur Isotopes; Thiourea