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Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model.

ABSTRACT: Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model. A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 mg/kg), SLN-CRYP (5 mg/kg), ABZ (50 mg/kg) DXM (0.5 mg/kg), and PHE (30 mg/kg). were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains. All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p < 0.0001); as were frequency (p < 0.0001) and duration (p < 0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p = 0.0016) and IFN-γ (p < 0.0001). Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

SUBMITTER: Mante PK

PROVIDER: S-EPMC8663984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveDiscordances between imaging findings of parenchymal neurocysticercosis and seizure expression have been reported, and as such the possibility that neurocysticercosis and seizures may frequently coexist by chance has been raised. In this study, we evaluate the topographic relationship between seizure foci based on semiology and electroencephalography with the location of parenchymal neurocysticercotic lesions.MethodsSeizure information, neuroimaging (computed tomography and magnetic resonance imaging [MRI]) and electroencephalographic data from three randomized clinical trials of individuals with parenchymal neurocysticercosis and focal seizures were analyzed. Blinded epileptologists defined a potential seizure onset zone and a symptomatogenic zone for each individual based on semiology. The topographic relationship between semiology, either lesion location or areas of perilesional edema on baseline MRI, and electroencephalographic abnormalities were assessed.ResultsFifty-eight patients with one or two parenchymal neurocysticercotic lesions were included in this study. From them, 50 patients (86%; 95% CI, 75%-93%) showed a clinical-topography relationship with the potential seizure onset zone, and 44 (76%) also with the symptomatogenic zone. From the eight patients with no topographic relationship, five had focal seizures 30 days before or after the baseline MRI and showed perilesional edema. All of these five patients showed a clinical-topography relationship between such seizures and an area of perilesional edema, making a total of 55 patients (95%; 95% CI, 85%-99%) with clinical-topography relationship when perilesional edema is considered. Most patients with focal epileptiform discharges (7/8, 88%) had a topographic association between electroencephalographic focality, the potential seizure onset zone and a cysticercotic lesion.ConclusionSeizure semiology and focal epileptiform discharges are topographically related to neurocysticercotic lesions in most patients. These data strongly support seizure origin in the cortex surrounding these lesions.

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Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model.

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