Effects of polycaprolactone-based scaffolds on the blood-brain barrier and cerebral inflammation.

Severe pathoanatomical and mechanical injuries compromise patient recovery and survival following penetrating brain injury (PBI). The realization that the blood-brain barrier (BBB) plays a major role in dictating post-PBI events has led to rising interests in possible therapeutic interventions through the BBB. Recently, the choroid plexus has also been suggested as a potential therapeutic target. The use of biocompatible scaffolds for the delivery of therapeutic agents, but little is known about their interaction with cerebral tissue, which has important clinical implications. Therefore, the authors have sought to investigate the effect of polycaprolactone (PCL) and PCL/tricalcium phosphate (PCL/TCP) scaffolds on the maintenance of BBB phenotype posttraumatic brain injury. Cranial defects of 3 mm depth were created in Sprague Dawley rats, and PCL and PCL/TCP scaffolds were subsequently implanted in predetermined locations for a period of 1 week and 1 month. Higher endothelial barrier antigen (EBA) expressions from PCL-based scaffold groups (p>0.05) were found, suggesting slight advantages over the sham group (no scaffold implantation). PCL/TCP scaffold group also expressed EBA to a higher degree (p>0.05) than PCL scaffolds. Importantly, higher capillary count and area as early as 1 week postimplantation suggested lowered ischemia from the PCL/TCP scaffold group as compared with PCL and sham. Evaluation of interlukin-1ß expression suggested that the PCL and PCL/TCP scaffolds did not cause prolonged inflammation. BBB transport selectivity was evaluated by the expression of aquaporin-4 (AQP-4). Attenuated expression of AQP-4 in the PCL/TCP group (p<0.05) suggested that PCL/TCP scaffolds altered BBB selectivity to a lower degree as compared with sham and PCL groups, pointing to potential clinical implications in reducing cerebral edema. Taken together, the responses of PCL-based scaffolds with brain tissue suggested safety, and encourages further preclinical evaluation in PBI management with these scaffolds.

Post-traumatic dynamic changes in the antibody titer against oxidized low density lipoproteins.

Oxidized low density lipoproteins (oLDL) are products of systemic oxidative stress initiated by the mechanism of free radical induced lipid peroxidation. Oxidatively modified epitopes on LDL molecules are immunogenic and antibodies against such epitopes are generated. The aim of the study was to determine whether traumatic injury and consequent oxidative stress are accompanied by changes in the titer of autoantibodies against oLDL, and to determine whether patients with different injuries can be distinguished by measuring their anti-oLDL titer. Sera of twenty-four patients divided into three groups of eight subjects each were investigated by an anti-oLDL ELISA immunoassay: 1) patients with bone fractures, 2) with traumatic brain injury (TBI) and 3) with both bone fractures and TBI. The patients were followed during four weeks after injury and anti-oLDL titers were determined on a weekly basis. The control group consisted of 22 healthy persons. The lowest antibody titer was measured in all groups during the 1st week after injury. While the serum levels of patients with combined injury did not differ from those of the other two groups, the levels of patients with TBI were significantly higher than those of patients with isolated bone fractures. During the four-week convalescence, a gradual and significant increase in the anti-oLDL titer was observed in all patients. However, this value was increased above normal values only in the sera of patients with TBI during the third and the fourth week after injury. Reactive oxygen species (ROS) play an important role in the regulation of bone synthesis and remodelling. Therefore, we assume that the combination of a fracture with TBI-mediated post-traumatic stress response might be related to the altered fracture healing (enhanced osteogenesis) frequently observed in these patients.

[Immune status dynamics in different lateralizations of focal traumatic brain lesions]. / Dinamika immunnogo statusa pri raznoi lateralizatsii travmaticheskikh ochagovykh porazhenii golovnogo mozga.

The changes occurring in the immunity of 118 patients with focal brain injuries verified at surgery and during computed tomography were studied in relation to hemispheric lateralization. Patients with left-sided brain injuries showed more severe abnormalities of immunity and had a considerable lot of pyoinflammatory complications, including extracerebral ones. In patients with right-sided brain injuries, compensation of the changed immune responses occurred more rapidly, but intracranial pyoinflammatory complications took place more frequently. The magnitude and changes in immunity were found to depend upon the hemispheric lateralization of focal brain injuries, which characterizes that the brain regions play unequal role in the formation of an immune response. Differences become significant at week 3 at the peak of secondary immunodeficiency.

[Nonspecific resistance and the immunological indices in brain contusion]. / Nespetsificheskaia rezistentnost' i nekotorye immunologicheskie pokazateli pri ushibe golovnogo mozga.

As many as 55 healthy persons and 69 victims with brain contusion of medium and severe degree were examined. Inhibition of cellular immunologic reactions and attenuation of nonspecific resistance as well as increase of immunoglobulins, immune complexes and cerebral antibodies were revealed. These changes were found to be more pronounced in a severe brain contusion.

Unusual anaphylatoxin dynamics after head injury--case report.

The case reported exemplifies a clinical picture markedly at variance with the chronology of symptoms and laboratory findings generally held to be typical in patients with post-traumatic shock. During a protracted clinical course this young man with a skull fracture and epidural haematoma experienced profound hypotension and adult respiratory distress syndrome (ARDS) well in advance of marked fourfold rise of circulating peripheral C3a desArg anaphylatoxin levels. This raises a note of caution with regard to diagnostic and/or therapeutic decisions based on anaphylatoxin assessment of neurosurgical trauma patients at risk of ARDS.