Delayed profound local brain hypothermia markedly reduces interleukin-1beta gene expression and vasogenic edema development in a porcine model of intracerebral hemorrhage.

White matter (lobar) intracerebral hemorrhage (ICH) can cause edema-related deaths and life-long morbidity. In our porcine model, ICH induces oxidative stress, acute interstitial and delayed vasogenic edema, and up-regulates interleukin-1beta (IL-1beta), a proinflammatory cytokine-linked to blood-brain barrier (BBB) opening. In brain injury models, hypothermia reduces inflammatory cytokine production and protects the BBB. Clinically, however, hypothermia for stroke treatment using surface and systemic approaches can be challenging. We tested the hypothesis that an alternative approach, i.e., local brain cooling using the ChillerPad System, would reduce IL-1beta gene expression and vasogenic edema development even if initiated several hours after ICH. We infused autologous whole blood (3.0 mL) into the frontal hemispheric white matter of 20 kg pentobarbital-anesthetized pigs. At 3 hours post-ICH, we performed a craniotomy for epidural placement of the ChillerPad. Chilled saline was then circulated through the pad for 12 hours to induce profound local hypothermia (14 degrees C brain surface temperature). We froze brains in situ at 16 hours after ICH induction, sampled perihematomal white matter, extracted RNA, and performed real-time RT-PCR. Local brain cooling markedly reduced both IL-1beta RNA levels and vasogenic edema. These robust results support the potential for local brain cooling to protect the BBB and reduce injury after ICH.

Unipolar recording and pacing using a conductive introducer sheath as the indifferent electrode.

Unipolar recording has been shown to have advantages over bipolar techniques in certain clinical settings. Unipolar recording and pacing, however, require an indifferent electrode to complete the circuit. Current options for the indifferent electrode require additional hardware or special recording capabilities. A novel percutaneous unipolar conductive introducer sheath (PUCIS) was developed for unipolar electrophysiological recording and pacing. This article describes the development of this sheath, in vitro testing results, and initial animal data using the PUCIS as the indifferent electrode. The current silver/gold coating has acceptable mechanical and electrical properties. Electrogram appearance and amplitude, pacing thresholds, and impedances were comparable to currently used alternatives. The PUCIS sheath may therefore serve as a convenient standard as the indifferent electrode for unipolar electrophysiology.

Feedback control of intracranial pressure using mannitol.

A discrete-time model describing intracranial pressure (ICP) dynamics is extended to account for changes in blood osmolarity due to an i.v. injection of mannitol. It includes the effect of a blood osmolarity change on cerebrospinal fluid (CSF) formation and absorption. In order to maintain the ICP at a desired lowered level, a control algorithm is constructed. The controller is designed by minimizing a performance criterion, which consists of the mean squared error between the measured ICP and desired ICP, and the squared input. Minimizing the performance criterion specifies the controller. For on-line implementation, an approximately optimal controller is suggested. Simulation results show the feasibility of using this controller to regulate ICP.