Title:The Pathogenesis of Neurotrauma Indicates Targets for Neuroprotective Therapies
Volume: 19
Issue: 8
Author(s): Jacek M. Kwiecien*
Affiliation:
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Room HSC 1U22D, 1280 Main Street West, Hamilton, ON, L4S 4K1,Canada
Keywords:
Neurotrauma, inflammatory phase of SCI, cavity of injury, arachnoiditis, astrogliosis, subdural infusion, neuroprotective
therapy, vasogenic edema.
Abstract: The spinal cord injury (SCI) initiates an extraordinarily protracted disease with 3 phases;
acute, inflammatory, and resolution that are restricted to the cavity of injury (COI) or arachnoiditis
by a unique CNS reaction against the severity of destructive inflammation. While the severity of
inflammation involving the white matter is fueled by a potently immunogenic activity of damaged
myelin, its sequestration in the COI and its continuity with the cerebrospinal fluid of the subdural
space allow anti-inflammatory therapeutics infused subdurally to inhibit phagocytic macrophage
infiltration and thus provide neuroprotection. The role of astrogliosis in containing and ultimately in
eliminating severe destructive inflammation post-trauma appears obvious but is not yet sufficiently
understood to use in therapeutic neuroprotective and neuroregenerative strategies. An apparent antiinflammatory
activity of reactive astrocytes is paralleled by their active role in removing excess
edema fluid in blood-brain barrier damaged by inflammation. Recently elucidated pathogenesis of
neurotrauma, including SCI, traumatic brain injury (TBI), and stroke, calls for the following principal
therapeutic steps in its treatment leading to the recovery of neurologic function: (1) inhibition
and elimination of destructive inflammation from the COI with accompanying reduction of
vasogenic edema, (2) insertion into the COI of a functional bridge supporting the crossing of regenerating
axons, (3) enabling regeneration of axons to their original synaptic targets by temporary safe
removal of myelin in targeted areas of white matter, (4) in vivo, systematic monitoring of the consecutive
therapeutic steps. The focus of this paper is on therapeutic step 1.
