Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Inflammasome: Its role in traumatic brain and spinal cord injury

“…After 6 hr of moderate experimental cervical SCI, NLRP1, and ASC immunoreactivity is significantly increased (de Rivero Vaccari et al, ). Co‐immunoprecipitations of post‐SCI spinal cord lysates with anti‐NLRP1 or anti‐ASC antibodies and pre‐immune serum also shows increased association of NLRP1, ASC, and caspase‐1 in the injured spinal cords at 24 hr after SCI (Lin et al, ). Finally, attenuation of NLRP1 expression by exogenous administration of heme oxygenase‐1 (HO‐1) in the SCI experimental model reveals reduction of the NLRP1 inflammasome‐induced neuronal cell death and improvement of functional recovery (Lin et al, ).…”

“…Inflammasome components depict a distinct and non‐overlapping disruption of the tissue that is involved (de Rivero Vaccari et al, ). The term pyroptosis is used for inflammasome‐mediated neuronal death (Lin et al, ) and consists of membrane pore formation, loss of membrane integrity, and osmotic swelling (Sagulenko et al, ). Pyroptosis allows further release of the inflammasome complex into the extracellular environment where the platform is capable of potentiating tissue inflammation (Barrington, Lemarchand, & Allan, ).…”

“…There seems no obvious activation of inflammasomes at the beginning of SCI, thus, necrosis and apoptosis are the predominant phenomena. Later on, inflammatory stress causes pyroptosis and apoptosis to increase the secondary injury (Lin et al, ). Rivero Vaccari et al () using moderate SCI injury at the vertebral level T8 and a TBI model found high levels of NLRP1 inflammasome protein expression in neurons.…”

Targeting axonal degeneration and demyelination using combination administration of 17β‐estradiol and Schwann cells in the rat model of spinal cord injury

“…1,3 A secondary insult causes a diffuse, long-lasting damage. 1,2 A primary insult results from exorbitant mechanical hit that is confined to the region of vertebral fracture, and it causes acute hemorrhage, necrotic cell death, and neuronal loss.…”

“…1,2 A primary insult results from exorbitant mechanical hit that is confined to the region of vertebral fracture, and it causes acute hemorrhage, necrotic cell death, and neuronal loss. 3 Unlike the peripheral nerve system (PNS), axonal regeneration capability in the central nerve system (CNS) is limited after injury, as in SCI, 4,5 thereby restricting restoration of communication between ascending and descending pathways, which further leads to permanent sensory and motor dysfunction. This is destructive to glial and neuron cells 3 and stimulates late cell death and extensive neurodegeneration followed by a noticeable expansion in the site of injury to the higher segments of the spinal cord.…”