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Project

Internal decompression of the damaged spinal cord promotes tissue sparing

Funder: Craig H Neilsen Foundation

Funding period
USD 600 K
Funding amount
Abstract
No treatment of SCI yields superior neurological outcomes than effective neuroprotection. However, SCI management lags behind that of brain injury due to a lack of real time physiological measures of critical parameters such as spinal cord blood flow (SCBF) and oxygenation in the critical penumbra between destroyed and preserved tissue. Current SCI management relies on raising MAP to 85 mmHg with IV vasoconstrictors to improve SCBF with no feedback of the efficacy of this intervention and with knowledge that elevated BP may be damaging in fragile post-SCI vasculature by promoting hemorrhage and vasogenic edema. The spinal cord undergoes swelling due to due to intracellular and extracellular edema and hemorrhage within the injury epicenter, and necrotic tissue and hemorrhage exert mass effect. The pia mater and the dura resist the increase in parenchymal volume leading to elevated spinal cord intraparenchymal pressure (SCIP). Further, unlike with brain injury there are no surgical interventions that address mass effect or toxicity due to necrotic tissue, hemorrhage, and progressive inflammation after SCI. Thus we propose to study the feasibility to monitor SCBF, SCIP, tissue oxygenation, swelling and pulsatility using laser Doppler, optical, thermal diffusivity, B-mode ultrasound and harmonic ultrasound contrast methods in a well standardized T9 minipig contusion model. Three hypotheses are tested, 1) Increasing SCIP progressively reduces SCBF to ischemic levels in spinal cord penumbra. 2) Spinal cord feedback regulated MAP is superior to fixed MAP. 3) The neuroprotective benefit of spinal cord internal decompression (SCID) is sufficient to improve walking and tissue sparing. We will determine whether the injury penumbra is better supported using fixed MAP 85mmHg or allowing MAP to be regulated based on recording the flow, pressure and oxygenation status of penumbra tissue 2-4 cm from the epicenter. When A) tissue pressure exceeds 25 mm Hg, B) the penumbra becomes progressively ischemic, or C) evoked potentials show a marked reduction, the pigs are randomized to either continued monitoring or undergo SCID- the pia will be opened at the swollen contusion site and necro-hemorrhagic debris allowed to self-expel. The tissue removed is assessed for viability to determine that this method is not destructive. A duraplasty is performed to support CSF flow and reduce scarring. Internal decompression and control animals survive for 3 months and are compared for neurological outcomes including walking, sensory perception, hypersensitivity, and bladder emptying. The spinal cords are assessed for tissue preservation using 11.7T MRI and the extent and phenotype of macrophages within injury cavities are assessed histologically as early removal of necrotic material such as myelin debris may favor tissue reparative macrophages. CSF and brain tissue are analyzed to determine if SCID exposes the entire subarachnoid space to prolonged inflammation. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Diagnostic Radiology

  • RCDC

    Spinal Cord Injury

  • RCDC

    Brain Disorders

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical