Neuroprotective effects of tryptanthrin in the rat model of transient focal cerebral ischemia

Abstract

Introduction: The inflammatory response to cerebral ischemia plays a crucial role in stroke outcome. This study focuses on the neuroprotective effects of tryptanthrin, a plant alkaloid with anti-inflammatory activity, in the rat model of focal cerebral ischemia (FCI).

Materials and Methods: The neurological status of animals was assessed at 4, 24, and 48 hours after FCI (1-hour occlusion of the left middle cerebral artery) in male Wistar rats; the infarct size was assessed 48 hours after reperfusion. Rats received intraperitoneal injections of 6 and 12 mg/kg tryptanthrin or vehicle (control group) 30 min and 23 and 47 hours after FCI. The effects of 12 mg/kg tryptanthrin on the IL-1β and TNFα levels in brain tissue, blood brain barrier (BBB) permeability, and cerebral edema were assessed 24 hours after FCI.

Results: Tryptanthrin administration at a dose of 12 mg/kg significantly reduced the neurological deficit and infarct size compared with the corresponding values in control rats. Tryptanthrin administration at a dose of 6 mg/kg was ineffective. The IL-1β and TNF-α levels in cerebral infarction focus, the Evans blue content in the left (affected) hemisphere, and water content in the supra- and subventricular structures of the affected hemisphere increased 24 hours after FCI. Tryptanthrin administration (12 mg/kg) significantly attenuated the TNF-α level in the cerebral infarction site. The values of BBB permeability and water content in the experimental group did not significantly differ from the corresponding values in sham-operated rats.

Conclusion: Obtained data suggested that tryptanthrin may be considered an agent with significant neuroprotective properties, which provides rationale for further studies of this compound as a potential neuroprotector with anti-inflammatory mechanism of action.

Graphical Abstract