membrane damage axonal disruption death neurons& glia
Ionic Dysregulation
excessive intracellular level of Ca+2 ions
mitochondrial damage, aberrant enzyme activation, changes in gene expression and apoptosis
V as cu lar& m icrov as cu latu re dis ru ption
action potential b lock ade lipid peroxidation
Ca+2 ions
activ ation of calpains, m itochondrial dysf u nction, free radical produ ction .
compression-contusion type
1、shearing 2、laceration 3、acute stretching 4、sudden acceleration deceleration
in
Secondary Injury Mechanism s
1 ：Immediate Phase (0–2 H ou rs)
glutamate rise
free radical reaction
ROS and RNS free radicals absorb an electron from a lipid molecule
lipid peroxidation
cell lysis, the dysfunction of organelles, calcium dyshomeostasis
demyelination of axons and loss of neurons
injury
Inflammatory Mediators Cellular Immune Response
infiltration of inflammatory cells
TNFα, interferons, aILs
Pathophysiology of SCI
Epidemiology of SCI
SCI
CONTENTS
Pathophysiology of SCI
Emerging Regeneration&Repair Strategies
Epidemiology of SCI
AGE ： The average age
inhibition of TNFα signaling
improve functional neurological recovery
S u b acu te P has e (2 D ays to 2 W eeks)
REGIONS : cervical spine
Pathophysiology of SCI
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Primary Injury Phas e
mechanical injury
Secondary Injury M echanism free s
VS
radical production
traumatic spinal cord
overexpression of TNF-α is deleterious in the acute phase, but beneficial in the chronic phase in the response to SCI
TNFα-deficient mice
from 28.7 to 37.6 years in the elderly from 4.7 to 10% SEX : male-to-female ratio is ~ 4 to 1
CAUSE : motor vehicle accidents (50%),
falls and work-related injuries (30%) violent crime (11%), sports-related injuries (9%)
activation of resident microglia.
astrocytes, microglia, T cells, neutrophils, invading monocytes.
increased apoptotic cells, lesion size, worsened functional recovery
necrotic apoptotic cell death
Excitotoxicity
influx of Na+ and Ca++
excessive activation of glutamate receptors extracellular glutamate rise
Neurons and oligodendrocytes
axon blood vessels
vascular dysfunction
edema
Ischemia
excitotoxicity electrolyte shifts
inflammation
cell membrane
cell death delayed apoptotic
Primary Injury Phas e
1
2
A cu te P has e（2 -4 8 hou rs)
3 S u b acu te P has e (2 D ays to 2 W eeks) 4 Interm ediate P has e (2 W eeks to 6 M onths)
5、chronic phase(≥6 months)
Im m ediate P has e 0 -2 hou rs
cell membrane& vascular & microvasspinal cord ischemia
glutamate
TNFα and IL-β
Early Acute Phase (2–48 H ou rs)