Minocycline attenuates cognitive impairment and restrains oxidative stress in the hippocampus of rats with chronic cerebral hypoperfusion

Abstract

Objective Nitric oxide (NO) was speculated to play an important role in the pathophysiology of cerebral ischemia. Minocycline, a tetracycline derivative, reduced inflammation and protected against cerebral ischemia. To study the neuroprotection mechanism of minocycline for vascular dementia, the influences of minocycline on expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were observed in the brains of Wistar rats. Methods The vascular dementia rat model was established by permanent bilateral common carotid arteries occlusion (BCCAO). Wistar rats were divideded into 3 groups randomly: sham-operation group (S group), vascular dementia model group (M group), and minocycline treatment group (MT group). The behaviour was tested with Morris water maze and open-field task. Expressions of iNOS and eNOS were measured by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The optical density value was measured by imaging analysis. Percentage of positive cells with iNOS and eNOS expression was analyzed with optical microscope. Results Minocycline attenuated cognitive impairment. Inducible NOS was significantly down-regulated in MT group, compared with that in M group (P < 0.01), while eNOS was significantly up-regulated, compared with that in M group (P < 0.01). The expressions of iNOS and eNOS in M and MT groups were higher than those in S group (P < 0.01). Conclusion Minocycline can down-regulate the expression of iNOS and up-regulate the expression of eNOS in vascular dementia, which restrains apoptosis and oxidative stress to protect neural function.

Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP

“…The increase in the expression of CD4+ cells observed in our study indicates that T cells are involved in VCI pathology. [26][27][28]32 We observed that minocycline had several beneficial effects compared with vehicletreated controls: treated animals survived 4 weeks longer, showed improvement in multimodal MRI, and behavior. The vehicle, DMSO, also prolonged survival, which is consistent with its positive effect on ischemia from its antioxidant effects, but the improvement in survival was not mirrored by MRI.…”

“…26 More recently, it has been studied in a number of neuroinflammatory conditions, and relevant to this study, it was shown to downregulate the expression of inducible nitric oxide synthase in a model of vascular dementia involving bilateral carotid artery occlusion in normotensive rats. 27,28 …”

Consensus statement for diagnosis of subcortical small vessel disease

“…150 Drugs that have been approved for other uses, for example, the anti-inflammatory agents and free radical scavengers, minocycline and simvastatin, all of which have been shown to have beneficial effects in animals models and could be tested in humans. 151,152 A biologic product, E-selectin, has been shown to reduce inflammation after induction of nasal tolerance in the hypertensive rat. 153 Reliable end points will need to be established.…”

Minocycline exerts a neuroprotective action against 6-OHDA-induced neurotoxicity: in vivo and in vitro studies

“…The neuroprotective effect of Mino (10 and 25 mg/kg) was observed after its intraperitoneal administration for 7 days. Although there are many studies showing the neuroprotective effects of Mino on various experimental models, such as cerebral ischemia [28,29,30,31] among others, those on PD models are fewer [32,33].…”