![]() The main driving factor for the carrying out of neuroinflammation is the bid to root out the damaging stimulus, however, once initiated it might become over activated, spreading initially to the damaged brain regions and initiating a range of intricate signaling pathways that advance the neuroinflammation to the next level ( 11, 12). Neuroinflammation comprises of complex cellular and sub-cellular mechanisms triggered in response to injury in brain cells ( 10). These molecular neuroinflammatory mechanisms potentiate damage to the brain cells and influence the clinical outcome. The instant and primary damage to the brain cells are followed by neuroinflammatory cascade entailing bursts of reactive oxygen species (ROS), release of a variety of signaling cytokines, and damage to the cerebral microvasculature, as well as disruption of the blood-brain barrier (BBB) ( 6– 9). In either of these cases, the repercussions are brain-tissue injury and functional disabilities due to damage to the respective brain region ( 5). Hemorrhagic stroke underscores the rupture of intracranial aneurysm (ICA), dural arteriovenous fistula (dAVF), cerebral arteriovenous malformation (AVM), or rupture of small vessel due to hypertension, while ischemic stroke represents embolic or thrombotic occlusion in a brain artery ( 3, 4). Stroke is generally classified into hemorrhagic and ischemic, with the latter involved in about 85% of stroke accidents ( 2). It is the leading cause of permanent disabilities ( 1). ![]() Stroke follows heart diseases and cancer as the highest global cause of mortality. This review article highlights important cellular and subcellular targets for stroke, and might aid the scientific community in deeply understanding and targeting one or more these targets, to develop clinical therapeutic interventions in stroke. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. That, too, has little to do with treating long-term post-stroke disabilities. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. Ischemic stroke is one of the leading causes of morbidity and mortality globally. 6Department of Neurosurgery, Faculty of Medicine and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.5Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.4Imran Idrees College of Pharmacy, Lahore, Pakistan.3Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan. ![]() 2Faculty of Pharmacy, University of Lahore, Lahore, Pakistan.1Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.Sherjeel Adnan 2, Awais Ali Zaidi 2,4, Daniel Hänggi 6 and Sajjad Muhammad 5,6*
0 Comments
Leave a Reply. |