: Intracerebral hemorrhage (ICH) is a devastating subtype of stroke associated with high morbidity and mortality that is considered a medical emergency, mainly managed with adequate blood pressure control and creating a favorable hemostatic condition. However, to date, none of the randomized clinical trials have led to an effective treatment for ICH. It is vital to better understand the mechanisms underlying brain injury to effectively decrease ICH-associated morbidity and mortality. It is well known that initial hematoma formation and its expansion have detrimental consequences. The literature has recently focused on other pathological processes, including oxidative stress, neuroinflammation, blood-brain barrier disruption, edema formation, and neurotoxicity, that constitute secondary brain injury. Since conventional management has failed to improve clinical outcomes significantly, various neuroprotective therapies are tested in preclinical and clinical settings. Unlike intravenous administration, intranasal insulin can reach a higher concentration in the cerebrospinal fluid without causing systemic side effects. Intranasal insulin delivery has been introduced as a novel neuroprotective agent for certain neurological diseases, including ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Since there is an overlap of mechanisms causing neuroinflammation in these neurological diseases and ICH, we believe that preclinical studies testing the role of intranasal insulin therapy in ICH are warranted.
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