SPINAL CORD INJURY:

INFLAMMATION, APOPTOSIS, and ROLE OF NGF

Shila Wisnasari (0810720065)

Mechanism of Spinal cord damage

Primary mechanical injury
Locally restricted acute hemorrhage and ischaemia

Secondary injury
Further destruction of neuronal and glial cells Expansion of the damage
Zhang, et al., 2012

Primary Injury
C1-C3 Breathing is dependant on a ventilator All daily functions must be totally assisted C4 Same as C1-C3 except breathing can be done without a ventilator C5 Good head, neck, shoulder movements, as well as elbow flexion C6 Wrist extension movements are good C7-C8 All hand movements

Primary Injury
T1-T4 (paraplegia) Normal communication skills T5-T9 Independent for personal care T10-L1 Partial paralysis of lower body L2-S5 Some knee, hip and foot movements with possible slow difficult walking with assistance or aids

Inflammation after SCI

Inflammation major component of secondary injury and may result in apoptosis of neurons and oligodendrocytes

Genovese, et al., 2009

Inflammation after SCI

The Intact Spinal cord

Moon and Gage, 2006

Spinal cord Injury

Spinal cord after injury

Moon and Gage, 2006

Inflammatory response after SCI

Obermair, et al., 2008

Cytokines involved in inflammatory response after SCI

TNF- Derived from macrophage Potentiate neuronal cell death mediates the recruitment of neutrophils and macrophages to sites of infection

Pineau & Lacroix, 2007

Cytokines involved in inflammatory response after SCI IL-6

Cytokines involved in inflammatory response after SCI

IL-6 IL-6 receptor monoclonal antibody treatment suppressed the astrocytic differentiation, decrease the number of inflammatory cells and the severity of connective tissue scar formation
Pineau & Lacroix, 2007

CNS inflammatory responses after SCI

Initiated by peripherally derived immune cells and activated glial cells T-cells activating macrophages B-cells unknown but maybe pathological Macrophage release inflammatory cytokines
Zhang, et al., 2012

Apoptosis after SCI

After SCI, some cells die by posttraumatic necrosis, others die by apoptosis A biochemical cascade activates protease that destroy molecules required for cell survival and others that mediate a program of cell suicide

Byrnes, et al., 2007

Role of caspase
Protease that regulates the apoptotic cell death program (Green, 1998) 3 caspase involved in SCI caspase 3, caspase 8, caspase 9 (Springer, et al., 1999)

Process of Apoptosis after SCI

Role of death receptor

Abbas, et al., 2008

Nerve Growth Factor (NGF) a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons (nerve cells).
NGF circulates throughout the entire body and is important for maintaining homeostasis.

Aloe, et al., 2012

 Clinical studies have shown that NGF can regenerate the peripheral nerve in rats shows promise for helping people who have been paralyzed because of spinal cord injuries.

NGF and SCI NGF can promote the repair of nerve after nerve injury EPO + NGF may contribute a reduction in demyelination within the spinal cord and reduce the inflammatory and decrease apoptosis
(Hassan & El-Rahim, 2013)