Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression

Area of Science:

• Neuroscience
• Physiology
• Biochemistry

Background:

• Stroke is a leading cause of disability, with brain edema and motor deficits being major complications.
• Exercise is a promising therapeutic strategy for stroke recovery, but its underlying mechanisms are not fully understood.

Purpose of the Study:

• To investigate the effects of forced treadmill exercise on ischemic brain edema and motor function after stroke.
• To elucidate the molecular mechanisms, including aquaporin 4 (AQP4) and Na+/H+ exchangers (NHEs), involved in exercise-induced recovery.

Main Methods:

• Wistar rats underwent transient middle cerebral artery occlusion (tMCAO) and were subjected to forced treadmill exercise.
• Brain edema was assessed using MRI, histochemistry, and tissue water content.
• Motor function was evaluated, and gene/protein expression of AQP4 and NHEs was analyzed.
• Pharmacological interventions with corticosterone, mifepristone, and spironolactone were employed.

Main Results:

• Exercise significantly reduced brain edema and improved motor function in tMCAO rats.
• Exercise prevented ischemia-induced upregulation of AQP4 and NHE mRNA.
• Corticosterone mimicked exercise effects, suppressing AQP4 and NHE1 expression in glial cells.

Conclusions:

• Forced treadmill exercise ameliorates ischemic brain edema and motor deficits post-stroke.
• The therapeutic effects are mediated, at least partly, by suppressed NHE1 and AQP4 expression, influenced by elevated corticosterone levels.