The effect of administration of minocycline on cerebral cortex of traumatic brain injury rat model

Abstract

Background: Traumatic brain injury (TBI) is a brain lesion that still remains high mortality and disability. Until now, there is no definite pharmacologic treatment for TBI. Activation of glial cells plays a pivotal role in various damage processes of the central nervous system (CNS). Minocycline, a tetracycline derivative, has been shown to inhibit the activation of microglia and reduce the brain damage in several models of brain lesions. Inhibition of microglial activation may halt neuronal damage, which is known to be due to the phenotype of microglia being inhibited. Purpose: We investigated changes in microglial activation and neuroprotection of cerebral cortex by administration of minocycline in the TBI model of rats.

Material and Methods: Male Spraque-Dawley rats, 6 to 9 weeks old with mean body weight of 250g, were used in this study. All experimental rats were exposed to a weight drop model. Immediately following the impact, rats received a 45mg/kg dose of minocycline or phosphate-buffered saline (PBS), 0.2ml/kg via an intraperitoneal injection. Rats subsequently received injections every 2 days. At 3 and 14 days after the injury, separate groups of brain injured rats and sham injured rats were sacrificed. Gross contusions, tissue loss, and cellular status were assessed using gross findings, Nissl staining, and immunohistochemistry (GFAP expression in astrocyte, Iba1 and iNOS expression in microglia). The neuroprotective effect and the change of microglial activation were studied after administration of minocycline. Result: Activation of astrocytes and microglia were induced in TBI rat model, and the activities of astrocytes and microglia were decreased in the minocycline treated group. In the minocycline treated group, Iba1 and iNOS positive microglia decreased compared to the control group. Conclusions: Collectively, our results suggest that injections of minocycline after TBI have potential therapeutic relevance, because they display anti-inflammatory functions that promote secondary neuroprotection by preventing activation of iNOS positive microglial activation.