Pharmacological potential of zonisamide and Nigella sativa per se and combination in high‐impact trauma device‐induced traumatic brain injury in Drosophila melanogaster

Abstract

Traumatic brain injury (TBI) is a public health menace responsible for millions of fatalities and disabilities. Numerous drugs available provide symptomatic relief but cannot stop the progress of secondary injury; thus, it is required to discover newer therapeutic agents that protect neuronal damage after trauma, predominantly in secondary injury. Thus the present study was designed to study the pharmacological potential of zonisamide and Nigella sativa (NS) per se and in combination, using high‐impact trauma device (HIT)‐induced TBI model in Drosophila melanogaster (fruit flies). Oregon R+ strains of fruit flies were pre‐treated, 24 h before TBI, with different concentrations of zonisamide, NS, and their combination. The mortality rate was observed at 0 h, 6 h, and 24 h, followed by measurement of locomotor activity using climbing assay after 6 h and 24 h of TBI. Furthermore, the level of AChE and various neurotransmitters were measured along with different oxidative stress parameters at 24 h after the injury. Administration of zonisamide and NS significantly reduced mortality rate and improved locomotor activity. Both zonisamide and NS elevate levels of AChE, GABA, serotonin, and dopamine level in fruit flies, along with a significant reduction in glutamate levels. Moreover, a concentration‐dependent elevation in SOD, GSH, and catalase level and a decrease in MDA and nitrite levels were observed. Co‐administration of zonisamide and NS showed tremendous neuroprotective potential by lowering behavior impairments, oxidative damages, and restoring altered neurotransmitter levels in fruit flies compared with individual administration and thus can employ as a better therapeutic medicine for the treatment of TBI.

Effect of zonisamide and Nigella sativa on blood-brain barrier permeability and neurological severity in traumatic brain injury-induced mice

“…Similarly, in our previous studies, both zonisamide and NS per se and combination significantly improves behavioral pattern and diminishes oxidative stress and neurotransmitters alteration in fruit flies following TBI 28 , along with a significant reduction in oxidative stress, glucose level, and blood pressure in mice following traumatic damage [29][30] , indicating that combination of both drugs can be a possible therapeutic intervention to reduce secondary damage triggered by traumatic injuries in the brain by preserving BBB integrity.…”