Modulation of the Blood-Brain Barrier Permeability in Neonatal Cytotoxic Brain Edema: Laboratory and Morphological Findings Obtained on Newborn Piglets with Experimental Pneumothorax

Abstract

Acute, bilateral pneumothorax (PT) was produced in 14 newborn piglets. The clinical status of the operated and 14 control animals was monitored by measuring the arterial blood gases, acid-base balance and mean arterial blood pressure. Different brain regions were processed for electron microscopy and albumin immunohistochemistry; water and electrolyte contents were also determined at the end stage of experimental intervention. Electron microscopy showed more intense pinocytotic activity in the endothelium of brain capillaries from PT animals evaluated by morphometry. Statistically significant (p < 0.01) differences were found in the distribution of pinocytotic vesicles in different brain areas of PT animals. The blood-brain barrier seemed to be impermeable to albumin in all brain regions both in the controls and in the PT group. Parallel with the changes observed in pinocytosis, the water and sodium contents were also increased in the PT group in the parietal cortex (water content 85.18 ± SD 0.81% vs. 84.10 ± SD 0.52%, p < 0.01; sodium content in wet brain tissue 70.94 ± SD 8.44 mmol/kg vs. 65.09 ± SD 4.43 mmol/kg, p < 0.05, in dry brain tissue 481.70 ± 75.70 mmol/kg vs. 410.15 ± SD 35.45 mmol/kg, p < 0.05) and in the cerebellum (water content 83.95 ± SD 1.08% vs. 83.02 ± SD 0.89%, p < 0.05; sodium content in wet brain tissue 60.67 ± SD 3.16 mmol/kg vs. 55.90 ± 6.26 mmol/kg, p < 0.01). However, in other brain regions – especially in the water-shed area – there was no correlation between the changes of pinocytosis and water-electrolyte contents of the tissues. It is suggested that the type of edema developing in this severe cardiovascular/hypoxic collapse is cytotoxic of origin and this fact should be more seriously taken into account in the treatment of the disease.

Impaired Early Neurologic Outcome in Newborn Piglets Reoxygenated with 100% Oxygen Compared with Room Air after Pneumothorax-Induced Asphyxia

“…The lower degree of damage observed in the pons in the asphyxiated animals might have originated from the better-maintained blood flow and oxygenation of the brain stem structures as compared with those of other brain regions during asphyxia. Moreover, a cerebral intraparenchymal sodium accumulation was demonstrated earlier in our neonatal pneumothorax model both in vitro (18,62) and in vivo (19,63).…”

“…The clinical status of the animals worsened continuously, and by the end of 1 h after the induction of pneumothorax, gasping, bradyarrhythmia, arterial hypotension, hypoxemia, and severe combined acidosis had developed. The pneumothorax was then relieved, and the response to therapy was controlled by transillumination (Wild M4000 fiberscope, Heerburgg, Switzerland) of the thorax (18,22,23). Asphyxiated animals were randomly divided into two groups.…”

A Swine Model of Neonatal Asphyxia

“…In comparison with our hypoxia protocol, combining hypercapnia with severe hypoxia will better simulate clinical asphyxia. Apart from alveolar hypoxia as in the current protocol, other approaches to induce hypoxia include the creation of pneumothorax 14 , halting mechanical ventilation 15 and the addition of carotid artery occlusion for cerebral ischemia. We attempt to make the hypoxia and reoxygenation clinically relevant.…”

Escherichia coli 0111 B4 Lipopolysaccharide Given Intracisternally Induces Blood-Brain Barrier Opening during Experimental Neonatal Meningitis in Piglets

“…Polyrnorphonuclear neutrophils augment but it are not essential for this early BBB abnormality (3,6). Previous observations suggest that increased NaF permeability is associated with an enhanced vesicular transport in brain capillary endothelium ( 14,18,25). It is also worthwhile to mention that it has been shown that polymyxin B, an endotoxin-neutralizing drug, improved the outcome of the experimentally induced bacterial meningitis (26).…”