Safety and feasibility of minocycline in treatment of acute traumatic brain injury.

BACKGROUND: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia. METHODS: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3-12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days. RESULTS: The mean initial GCS was 5.6 for Tier 1 patients and 5.4 for Tier 2. The Disability Rating Scale (DRS) had a trend towards improvement with the higher dose 12.5 SD ± 7.7 (N = 5) for Tier 1 at 4 weeks and 8.5 SD ± 9.9 at week 12 (N = 5), whereas for Tier 2 it was 9.7 ± 6.9 (N = 6) for week 4 and 6.0 SD ± 6.1 (N = 7) for week 12 (p = .251 repeated measures ANOVA). Liver function tests increased but resolved after the first week and there were no infections. CONCLUSIONS: Minocycline was safe for moderate to severe TBI at a dose twice that as recommended for treatment of infection. The higher dose did trend towards an improved outcome.

MR imaging of the yucatan pig head and neck vasculature.

PURPOSE: To evaluate the cerebral venous drainage system of the swine as a probable model to test whether extracranial venous abnormalities may play a role in neurodegenerative diseases as reported recently in multiple sclerosis. MATERIALS AND METHODS: Three Yucatan micropigs, 5 to 7 months old, were scanned with a comprehensive MRI protocol at 3 Tesla. The vascular anatomy of the head and neck was imaged using conventional and angiographic MR sequences. Phase-contrast MR images were collected at multiple levels of the neck and intracranial space to monitor flow. RESULTS: Three large cervical veins were observed; the external jugular vein draining the olfactory and gustatory tissues; the internal jugular vein (IJV) draining the cavernous sinus as well as surrounding soft tissues in the neck; and the ventral vertebral venous plexus (VVVP) surrounding the dural sac and paraspinal region. The majority of the cerebral blood flow in the pig appears to drain through the VVVP. Flow through the IJV comprised a nondominant component. Anastamoses were observed connecting the major veins of the neck bilaterally. CONCLUSION: The dominance of outflow from the brain to the VVVP may be analogous to the typical dominance of the IJVs in humans in the supine position.

Lipopolysaccharide-induced inflammatory cytokine production by Schwann's cells dependent upon TLR4 expression.

Signaling of Toll-like receptor-4 (TLR4) through its cognate ligand endotoxin appears critical in tissue inflammation associated with bacterial infection. We found that anti-GM1 antibody (Ab) enhances TLR4 expression in Schwann's cells (SCs) in vivo and in vitro. The anti-GM1 Ab-treated SC also showed increased release of pro-inflammation cytokines IL-1beta and TNF-alpha after incubation with lipopolysaccharide (LPS). Furthermore, down-regulation of TLR4 expression using antisense oligonucleotides targeted to TLR4 mRNA suppressed cytokine production in LPS stimulated cultures. These findings suggest that elevation of TLR4 expression increases sensitivity of SC to LPS and production of inflammatory mediators that may be responsible for peripheral nerve dysfunction.