A neuroprotective role of TRPM2 channel blocker and ROCK2 inhibitors to
curtail epileptogenesis in an experimental model of traumatic brain
injury.
Abstract
Background and Purpose: Post-traumatic epilepsy is the confirmed
progression of unprovoked seizures after head trauma in the general
population. This study was designed to control the devastating chronic
consequences of post-traumatic epileptogenesis. Experimental Approach:
Cerebral trauma was experimentally induced in Wistar rats to challenge
the seizure susceptibility for futuristic PTE. The efficiency of
Flufenamic acid, and fasudil hydrochloride, were assessed and compared
with valproic acid for abnormal neurobehavioural symptoms, biomolecular
levels, and apoptotic changes through histopathology. Key Results:
Initial brain insult was successfully exacerbated the normal
pathophysiology and neurobehavior changes in an experimental model. The
lowered seizure threshold confirmed the epileptogenesis progression when
a jab of Pentylenetetrazol(35mg/kg), gave the first successive seizure.
Disrupted BBB permeability, neuronal infarction, and brain edema were
found restored to normal after the treatment when compared to disease
controls. The altered levels of neurotransmitters, mitochondrial
complexes, cytoplasmic biomolecules/cytokines, different genes, and
channel proteins were also restored to normal after 14-days treatments.
No seizures have been observed with the test dose of Pentylenetetrazol.
We analyzed the histopathological changes of hippocampus/cortex regions
and found a significant decrease in the count of non-evident nucleoli,
nuclear pyknosis, vascular congestion, and perineural vacuolization in
treatment groups compared to injury controls. Conclusion and
Implications: All the drugs greatly minimized the epileptogenesis
cascade of futuristic PTE, confirms their neuroprotective capabilities.
Flufenamic acid was found more effective with many potential abilities
to minimize epileptogenesis compared to fasudil hydrochloride but its
combination with valproic acid has much neuroprotection and efficacy.