Volume-dependent modulation of cerebral cortex Na+,K + -ATPase activity and blood-brain barrier permeability by acute...

The Na+,K + -ATPase (NKA) enzyme is crucial for maintaining neuronal excitability, yet its response to acute physical exertion in the central nervous system remains largely unexplored. Here, we report a volume-dependent modulation of NKA activity in the cerebral cortex of rats subjected to a strenuous swimming protocol. A single bout of exhaustive exercise (1 set) significantly decreased total NKA activity and increased blood-brain barrier (BBB) permeability (albumin extravasation) without altering lipid peroxidation. Conversely, repeated exposure (3 sets, 72-h intervals) triggered an acute compensatory response: it prevented BBB disruption and significantly upregulated total NKA, α1, and α2/3 isoform activities. This functional upregulation occurred independently of total NKA protein expression but was accompanied by increased p-PKC/PKC and p-CaMKII/CaMKII phosphorylation ratios. These findings indicate that while an initial bout of exhaustive exercise compromises cortical NKA activity and neurovascular integrity, recurrent acute exertion induces rapid neuroprotective and enzymatic adaptations driven by post-translational kinase signaling.