Abstract Rationale Patients with acute ischemic stroke (AIS) frequently require mechanical ventilation during intensive care. However, inappropriate ventilatory strategies may exacerbate neuroinflammation and aggravate secondary brain injury. This phenomenon likely involves activation of glial cells both ipsilateral and contralateral to the primary lesion, as well as increased blood-brain barrier (BBB) permeability, reflected by elevated cerebrospinal fluid (CSF) protein content. We hypothesized that injurious mechanical ventilation promotes further brain damage via glial activation and BBB disruption in experimental focal AIS. Methods Twenty-four male Wistar rats were subjected to focal AIS induced by thermocoagulation of pial vessels. After 24 hours, animals were mechanically ventilated for 2 hours with identical tidal volume (6 mL/kg) and FiO2 = 0.25, but different PEEP levels: 3 cmH2O (protective), 9 cmH2O, or 11 cmH2O. Arterial blood gases and respiratory mechanics were assessed at baseline and at the end of ventilation. CSF was collected by cisterna magna puncture. Brains and lungs were harvested for immunohistochemistry and RT-PCR analysis. Results PaO2/FiO2 decreased over time across all groups (p 0.001). Peak, plateau, and driving pressures were higher with PEEP = 11 cmH2O (p 0.001 for all). In the lung, expression of TNF-α, IL-6, IL-1β, SP-B, and VCAM-1 was significantly higher in the 11 cmH2O group than in the 3 cmH2O group (p = 0.009, p = 0.003, p = 0.007, p = 0.002, p = 0.027, respectively) along with increased alveolar heterogeneity (1.30±0.08 vs 1.06±0.01, p = 0.002). In the brain, IL-1β and ZO-1 expression increased in the contralateral hemisphere but decreased ipsilaterally in 11 cmH2O group compared with PEEP of 3 cmH2O (p = 0.027 and p = 0.002, respectively), while HMGB-1 expression decreased bilaterally (p 0.01 for both). In the ipsilateral perilesional area, ramified Iba-1+ microglia (homeostatic) predominated in the 3 cmH2O group, whereas amoeboid Iba-1+ microglia (activated) was observed in the 11 cmH2O group. Furthermore, astrocytes increased surrounding perilesional area ipsilaterally in both 9 and 11 cmH2O compared with 3 cmH2O. Conversely, NeuN+ neuronal density was higher in the 3 cmH2O group, which denotes mature neurons. CSF protein concentrations were elevated in all ventilated animals (∼2 µg/µL) compared with physiological values (∼0.5 µg/µL). Conclusion Injurious mechanical ventilation with high PEEP levels exacerbated brain injury after focal AIS, possibly through BBB disruption and glial cells activation. In contrast, protective ventilation preserved neuronal integrity within the perilesional ischemic area. These findings highlight the critical interplay between lung and brain during mechanical ventilation after AIS. This abstract is funded by: FAPERJ, CNPq, CAPES
Silva et al. (Fri,) studied this question.