Epilepsy is a serious
brain disorder with diverse seizure types and
epileptic syndromes.
AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione (
NBQX) attenuates spontaneous recurrent
seizures in rats. However, the anti-epileptic effect of
NBQX in chronic
epilepsy model is poorly understood. Perineuronal nets (PNNs), specialized extracellular matrix structures, surround
parvalbumin-positive inhibitory interneurons, and play a critical role in neuronal cell development and synaptic plasticity. Here, we focused on the potential involvement of PNNs in the treatment of
epilepsy by
NBQX. Rats were intraperitoneally (i.p.) injected with
pentylenetetrazole (PTZ, 50 mg/kg) for 28 consecutive days to establish chronic
epilepsy models. Subsequently,
NBQX (20 mg/kg, i.p.) was injected for 3 days for the observation of behavioral measurements of
epilepsy. The Wisteria floribundi
agglutinin (WFA)-labeled PNNs were measured by immunohistochemical staining to evaluate the PNNs. The levels of three components of PNNs such as
tenascin-R,
aggrecan and
neurocan were assayed by Western blot assay. The results showed that there are reduction of PNNs and decrease of
tenascin-R,
aggrecan and
neurocan in the medial prefrontal cortex (mPFC) in the rats injected with PTZ. However,
NBQX treatment normalized PNNs,
tenascin-R,
aggrecan and
neurocan levels.
NBQX was sufficient to decrease
seizures through increasing the latency to
seizures, decrease the duration of seizure onset, and reduce the scores for the severity of
seizures. Furthermore, the degradation of mPFC PNNs by
chondroitinase ABC (ChABC) exacerbated
seizures in PTZ-treated rats. Finally, the anti-epileptic effect of
NBQX was reversed by pretreatment with ChABC into mPFC. These findings revealed that PNNs degradation in mPFC is involved in the pathophysiology of
epilepsy and enhancement of PNNs may be effective for the treatment of
epilepsy.