Arterial hypotension triggers perifocal depolarizations and aggravates secondary damage in focal brain injury.

Perifocal depolarizations (PFD) have been observed after traumatic brain injury, are known to disturb cerebrovascular reactivity and thus may contribute to the morphological consequences of brain injury. In this investigation, the role of PFD was studied in focal brain lesions with/without induction of delayed hypotension. Cerebral freeze lesions were induced in anesthetized normotensive rats that underwent perfusion fixation of brains 5 min, 4 h or 24 h after lesioning, respectively, to obtain quantitative histopathology. In additional groups, a 45-min period of moderate hypobaric hypotension was applied 15 min post-trauma and brains were perfusion fixed after 4 h or 24 h. In a second series, the direct current (DC) potential and cortical laser-Doppler flow (LDF) were measured adjacent to lesions under normotensive or hypotensive conditions. Sham procedures were carried out in rats that underwent hypotension alone. Lesioning resulted in a significant LDF decrease to 50% of baseline, further decreased during hypotension to less than 40% of control (P < 0.05). Sham animals had LDF values between 60 and 70% of control when subjected to hypotension. Focal brain injury always induced a negative DC shift shortly after lesioning. In 6 of 8 rats that underwent cold lesion plus hypotension, a second PFD was observed approximately 2.5 min after onset of hypotension accompanied by a relative LDF increase by 25 +/- 12%. Lesion expansion was significantly worsened by hypotension (8.19 +/- 0.56 mm(3) at 24 h) compared with normotensive rats (7.01 +/- 0.3 mm(3) at 24 h, P < 0.01). We conclude that hypotension triggers depolarizations by an ischemic mechanism that contributes to final tissue damage.

Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response.

The majority of trigeminal ganglia (TGs) are latently infected with alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the TGs, VZV reactivates very rarely. The goal of this study was to determine whether herpesvirus latency is linked to a local immune cell infiltration in human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive macrophages were found in 30 of 42 examined TGs from 21 healthy individuals. The presence of immune cells correlated constantly with the occurrence of the HSV-1 latency-associated transcript (LAT) and only irregularly with the presence of latent VZV protein. In contrast, uninfected TGs showed no immune cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma, tumor necrosis factor-alpha, IP-10, and RANTES transcripts were significantly induced in TGs latently infected with HSV-1 but not in uninfected TGs. The persisting lymphocytic cell infiltration and the elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for the first time that latent herpesviral infection in humans is accompanied by a chronic inflammatory process at an immunoprivileged site but without any neuronal destruction. The chronic immune response seems to maintain viral latency and influence viral reactivation.