Neuroprotective efficacy of 4-Hydroxyisoleucine in experimentally induced intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a severe form of brain injury, which is a major cause of mortality in humans. Hydrocephalus and cerebral hematoma lead to severe neurological deficits. A single autologous blood (ALB) injection in rats' brains induces hemorrhage and other conditions that regularly interfere with the standard treatment of several cellular and molecular pathways. Several studies have found that IGF-1/GLP-1 decreases the production of inflammatory markers in peripheral tissues, while some have found that they also have pro-inflammatory functions. Since these receptors are down-regulated in hemorrhagic situations, we looked into the potential neuroprotective effect of 4-hydroxyisoleucine (4-HI); 50 mg/kg and 100 mg/kg, an active compound Trigonellafoenum-graecum, on post-hemorrhagic deficits in rats. Long-term oral administration of 4-HI for 35 days has improved behavioral and neurochemical deficits and severe pathological changes and improved cellular and molecular markers, apoptotic markers in the ALB-induced ICH experimental model.Furthermore, the findings revealed that 4-HI also improved the levels of other neurotransmitters (Ach, DOPA, GABA, glutamate); inflammatory cytokines (TNF-alpha, IL-1β, IL-17), and oxidative stress markers (MDA, nitrite, LDH, AchE, SOD, CAT, GPx, GSH) in the brain when evaluated after Day 35. There is no proven treatment available for the prevention of post-brain hemorrhage and neurochemical malfunction; available therapy is only for symptomatic relief of the patient. Thus, 4-HI could be a potential clinical approach for treating post-brain haemorrhage and neurochemical changes caused by neurological damage. Furthermore, 4-HI may be linked to other standard therapeutic therapies utilized in ICH as a potential pharmacological intervention.

Keywords

• Autologous blood
• Intracerebral hemorrhage
• IGF-1/GLP-1
• Hematoma
• 4-hydroxyisoleucine
• Apoptosis