Pathophysiology of Neurological Canine Distemper in Urban Dog Populations and the Pharmacological Basis of Neuroprotective Intervention in Lagos State

Canine distemper virus infection remains highly prevalent in the large urban dog population of Lagos State, South West Nigeria, where vaccination coverage is inadequate. Neurological distemper, representing central nervous system invasion by the morbillivirus, leads to demyelination, encephalitis, and chronic neurological sequelae that are largely irreversible with current supportive therapy. The pathophysiological cascade mediating neuronal injury in canine distemper includes glial activation, oxidative stress, excitotoxicity, and apoptosis, presenting multiple pharmacological intervention targets. This study combined in vivo clinical characterisation with in vitro mechanistic investigation to define the pathophysiology of neurological distemper in Lagos urban dogs and evaluate the neuroprotective potential of N-acetylcysteine, riluzole, and minocycline as adjunct therapies. Fifty dogs with confirmed neurological distemper by cerebrospinal fluid RT-PCR and clinical scoring were enrolled from veterinary hospitals across Lagos. Cerebrospinal fluid and serum were analysed for distemper viral load, cytokine profiles, oxidative stress markers, and neurofilament light chain as a neurodegeneration biomarker. Dogs were randomised to standard supportive care alone or supplemented with N-acetylcysteine, riluzole, or minocycline for 21 days. Canine choroid plexus cell cultures were infected with field isolates and treated with candidate neuroprotectants to characterise mechanism of action. CSF neurofilament light chain correlated significantly with distemper severity score and predicted mortality at 30 days. Minocycline significantly reduced CSF IL-1 beta and attenuated glial fibrillary acidic protein elevation in treated dogs compared with controls. N-acetylcysteine reduced CSF malondialdehyde. Survival rate at 30 days was significantly higher in minocycline-treated dogs. These findings establish the first controlled evidence for adjunct neuroprotective pharmacotherapy in canine distemper in Nigeria and open a translational avenue for clinical protocol development. Keywords: canine distemper, neuroprotection, minocycline, pathophysiology, Lagos.