Minocycline Synergizes with N-Acetylcysteine and Improves Cognition and Memory Following Traumatic Brain Injury in Rats

Background: There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Methodology/Principal Findings: Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Coadministration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when th

A simple solution for navigated placement of CSF catheters in slit-like or displaced ventricles

Introduction: For cases of slit-like ventricles we report of a simple solution for accurate placement of CSF catheters using neuronavigation.Methods: We developed a navigated stainless steel tube for accurate ventricular catheter placement. Feasibility of the tube in an experimental condition was investigated. Navigated ventricular catheter placement was performed in four patients. Cranial CT scans were acquired to plan the optimal trajectory for a catheter placement within a workstation. Intra-operatively, the CSF catheter was placed via the navigated tube mounted in a rigid position. CT scans were performed to prove correct catheter positioning. Results: Integration of the tube within the navigation procedure was accurate compared to the pointers orientation. In all patients the correct placement of the ventricular catheter was achieved instantly. Post-operative CT imaging verified ideal catheter position. Conclusion: The navigated tube is a simple and easy-to-use solution for exact catheter placement assisted by neuronavigation