Glimepiride treatment in collagenase-induced ICH mice improved neurological function and reduced edema, hematoma volume, BBB leakage, neuroinflammation, and neuronal apoptosis via modulation of tight junction proteins, MMP-9, inflammatory markers, and apoptosis regulators.

As an approved antidiabetic with reported neuroprotective effects, glimepiride's ability to preserve BBB integrity and dampen inflammation points to repurposing opportunities targeting mechanisms (BBB disruption, inflammation, cell death) that are relevant to Parkinson's disease neuroprotection,…

BACKGROUND: Intracerebral haemorrhage (ICH) is characterised by high mortality and lethality with no effective treatment. Studying the pathophysiological mechanism of brain injury after ICH is expected to improve prognosis. Glimepiride (GPD) has neuroprotective effects in ischaemic stroke and Parkinson's disease models. However, it is unclear whether GPD effectively reduces brain injury after ICH. Therefore, we evaluated GPD in acute brain injury in ICH mice and assessed its potential mechanisms. METHODS: C57BL/6 mice were injected with collagenase into the right striatum to induce ICH, and were euthanized after 3 days of GPD treatment (4 mg/kg/day). Brain tissues around the haematoma were collected for Western blot and microscopy analyses. The corner turn test, forelimb placing test and modified Garcia test were used to assess neurological functions during life. RESULTS: The effectiveness of GPD was demonstrated by improved neurological functions, decreased brain oedema and reduced haematoma volume. GPD upregulated ZO-1 and occludin expression while downregulating MMP-9, indicating that GPD protected the integrity of the blood-brain barrier. This was corroborated by the reduction of albumin and Evans blue leakage into the brain parenchyma of GPD-treated mice. Moreover, the anti-inflammatory efficacy of GPD was suggested by reduced Iba-1 and myeloperoxidase immunohistochemistry. GPD also decreased neuronal apoptosis, as evidenced by the upregulation of BCL-2, downregulation of BAX, and decreased number of TUNEL-positive cells. CONCLUSION: In ICH injury, GPD protects the integrity of the blood-brain barrier, alleviates neuroinflammation, improves neurological functions, mitigates brain oedema, lessens haematoma volume, and inhibits the apoptosis of neural cells.