DIFFERENTIAL LUNG INJURY AFTER PERMANENT AND TRANSIENT FOCAL CEREBRAL ISCHEMIA IN RATS

Major cerebral artery occlusion causes acute ischemic stroke and triggers systemic responses that extend beyond the brain, including lung injury. While arterial recanalization limits neuronal damage, reperfusion may also modulate peripheral organ dysfunction. In this study, we compared the pulmonary mechanical, structural and inflammatory consequences of permanent versus transient focal cerebral ischemia. Young male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion for 3 days (N = 10), transient occlusion for 60 minutes followed by 3 days of reperfusion (N = 9), or sham operation (N = 10). Lung injury was assessed by measuring respiratory mechanics by forced oscillation at positive end-expiratory pressures of 0, 3, and 6 cmH 2 O, histology, wet-to-dry ratio, bronchoalveolar lavage fluid (BALF) and serum cytokine profiling. Permanent ischemia increased respiratory tissue damping and elastance accompanied by pronounced alveolar septal thickening, fibrin deposition, pulmonary edema, hemoconcentration, and systemic inflammatory alterations. Conversely, transient ischemia showed similar respiratory mechanical changes or lung injury evidenced by histological and inflammatory responses, with tissue mechanical parameters remaining close to sham values. Several inflammatory and tissue remodeling markers were differentially regulated in serum and BALF, indicating compartment-specific lung responses. Moreover, the extent of cerebral ischemia correlated with deterioration of lung tissue mechanics. These findings demonstrate that persistent cerebral ischemia promotes lung injury triggered by adverse secondary alveolar inflammatory and structural changes, whereas transient cerebral ischemia is associated with milder pulmonary tissue damage. These findings highlight that the temporal dynamics of cerebral ischemia is an important determinant of stroke-associated lung injury.