Abstract
Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1β, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1β, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.
Highlights
Epilepsy is defined as the second most common neurological condition characterized by sudden recurrent episodes of epileptic seizures unprovoked by any immediately identifiable cause and is manifested clinically by abnormal behavior changes due to aberrant electrical discharges of set neurons in the brain [1]
Ltd., Chandigarh, India), which were employed for the present study and which were ethically approved by the institutional animal ethics committee and carried as per the guidelines of the Committee for Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Environment and Forest, Government of India
Our data provided the evidence of pharmacological modulation inflammatory mediators and antioxidant elements under chronic seizures, which have of inflammatory mediators and antioxidant elements under chronic seizures, which have been suggested to provide neuroprotective effects during epileptic seizures by attenuating been suggested to provide neuroprotective effects during epileptic seizures by attenuatthe kindling severity score induced by PTZ
Summary
Epilepsy is defined as the second most common neurological condition characterized by sudden recurrent episodes of epileptic seizures unprovoked by any immediately identifiable cause and is manifested clinically by abnormal behavior changes due to aberrant electrical discharges of set neurons in the brain [1]. An epileptic seizure is the clinical manifestation of an abnormal and excessive electrical discharge of a set of neurons in the brain [2]. The available antiepileptic drugs in many patients are quite successful in preventing the recurrence of these seizures, and they have been shown to provide a remarkable improvement in the clinical condition of some patients. None of the available drugs conclusively addresses the problem of containing the progressive increase in seizure severity, a process by which a near-normal brain turns epileptic
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