Minocycline Attenuates Brain Edema, Brain Atrophy and Neurological Deficits After Intracerebral Hemorrhage
Evidence suggests that microglia activation contributes to brain injury after intracerebral hemorrhage (ICH). The present study aimed to determine if minocycline, an inhibitor of microglia activation, can reduce brain edema, brain atrophy and neurological
- PDF / 529,700 Bytes
- 4 Pages / 595.276 x 790.866 pts Page_size
- 47 Downloads / 215 Views
Abstract Evidence suggests that microglia activation contributes to brain injury after intracerebral hemorrhage (ICH). The present study aimed to determine if minocycline, an inhibitor of microglia activation, can reduce brain edema, brain atrophy and neurological deficits after ICH. Male Sprague-Dawley rats received an infusion of 100-µL autologous whole blood into the right basal ganglia. Rats received minocycline or vehicle treatment. There were two sets of experiments in this study. In the first set of experiments, the effects of minocycline on ICH-induced brain edema were examined at day 3. In the second set, behavioral tests were performed at days 1, 3, 7, 14 and 28. Rats were killed at day 28 for brain atrophy measurement (caudate and lateral ventricle size). Minocycline reduced perihematomal brain edema in the ipsilateral basal ganglia (78.8 ± 0.4 vs. 80.9 ± 1.1% in the vehicle-treated group, p < 0.01). Minocycline also improved functional outcome. In addition, minocycline reduced brain tissue loss in the ipsilateral caudate (p < 0.01) and ventricular enlargement (p < 0.05). In conclusion, minocycline attenuates ICH-induced brain edema formation, neurological deficits and brain atrophy in rats suggesting an important role of microglia in ICH-related brain injury.
infiltration develops within 2 days in rats and activated microglial cells persist for a month (3,5). Microglia are cells within the brain that are activated in response to injury. Depending upon specific conditions they can have neurotrophic or neurotoxic actions (10). Activated microglia are associated with ischemic and hemorrhagic brain injury including intracerebral hemorrhage (ICH), and there is evidence that microglia contribute to ICH-induced brain damage (3,17). Inhibition of microglia activation with tuftsin fragment 1-3 reduces brain damage after ICH (15). Minocycline, a second generation tetracycline-based molecule, is a potent inhibitor of microglia activation (13). It is a highly lipophilic compound and penetrates the brainblood barrier easily (7). Minocycline has been reported to provide neuroprotection by inhibiting microglia. An in vitro study showed that minocycline reduced excitotoxicity in primary neuronal culture by preventing excitotoxin-induced microglial proliferation (12). It also inhibits macrophage/ microglia activation after ICH in the rat (8,16). In this study, we examined the effects of minocycline on brain edema formation, neurological deficits and brain atrophy in rat ICH model.
Keywords Brain atrophy • brain edema • cerebral hemorrhage • minocycline
Materials and Methods
Introduction
Animal Preparation and Intracerebral Injection
Inflammation aggravates hemorrhagic brain injury. An inflammatory response in the surrounding brain occurs shortly after ICH and peaks several days later (2). Neutrophil G. Xi (*), J. Wu, S. Yang, Y. Hua, W. Liu, and R.F. Keep R5018 Biomedical Science Research Building, Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA e-mail: g
Data Loading...
