Changes in substance P and NK1 receptor immunohistochemistry following human spinal cord injury

Abstract

Study design: An immunohistological assessment of substance P (SP), its NK1 receptor and claudin-5 in human spinal cord injury (SCI) tissue. Objective: To determine whether SP and NK1 receptor immunoreactivity are altered following human traumatic SCI. Setting: Australia. Summary of background data: SP has been implicated in the development of neurogenic inflammation and subsequent edema development following both traumatic brain injury and ischemic stroke. In these conditions, inhibition of its NK1 receptor has been shown to be neuroprotective as reflected in a reduction of edema and improved functional outcome. However, the role of SP following human SCI has not yet been assessed. Methods: Archived human SCI tissue was grouped according to survival times: control (no injury; n ¼ 5); immediate (death within an hour of the incident; n ¼ 6); 2-5 h (n ¼ 3); 3 days (n ¼ 5); 1 week (n ¼ 3); and 3-4 weeks (n ¼ 6). Sections were assessed for SP, its NK1 receptor and claudin-5 using immunohistochemical techniques. Results: Following SCI, dorsal horn SP immunoreactivity demonstrated a profound decrease compared with control tissue, indicating the loss of SP with SCI. A marked increase in perivascular NK1 staining was demonstrated after SCI compared with control levels. No obvious change in claudin-5 immunoreactivity was present immediately following injury, however, by 1 week post-SCI, decreased levels were noted. Conclusion: This study demonstrates that severe acute traumatic human SCI results in decreased SP and an immediate increase in NK1 receptor immunoreactivity, suggesting that there is a neurogenic inflammatory component following human SCI.

Substance P stimulates proliferation of spinal neural stem cells in spinal cord injury via the mitogen-activated protein kinase signaling pathway

“…Also, Pfenninger et al [44] reported different gene expressions and proliferations between adult spinal cord ependymal cells and subventricular zone-originated neural precursor cells. Recently, Leonard et al [45] demonstrated that the NK1R in the human spinal cord increased after SCI, and traumatic SCI could promote NSPC proliferation [12]. Therefore, we investigated whether SP has a role in proliferation of NSPCs in SCI.…”

“…The neurogenic response after SCI was thought to be an endogenous self-healing response of the adult spinal cord. Recently, Leonard et al [45] demonstrated that the NK1R in the human spinal cord increased after SCI. The present study demonstrated that SCI-induced SP expression (Fig.…”

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model

“…This idea was based on recent experimental data. First, central nerve damage appears to induce systemic release of substance P or calcitonin-gene-related peptide (CGRP) [ 35 , 36 ] which triggers pro-inflammatory mechanisms and neuronal regeneration [ 37 , 38 ]. Moreover substance P can be distally released from sensory nerves expressing the transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor, leading to the recruitment of activated platelets, mast cells and neutrophils, which is one inductive step necessary to injury acquired HOs [ 25 – 27 , 39 ].…”

The Role of Substance P in Secondary Pathophysiology after Traumatic Brain Injury

“…In studies of TBI, inhibition of posttraumatic neurogenic inflammation by prior depletion of sensory neuropeptides using chronic capsaicin pretreatment attenuated increased BBB permeability, and the development of edema and functional deficits (60, 61), with subsequent studies demonstrating that ACE inhibitors exacerbated histological damage and functional deficits after TBI (62). Further studies in stroke established that reversible ischemic stroke resulted in increased brain perivascular immunoreactivity to SP with associated edema formation (63), while decreased SP immunoreactivity in association with increased NK1 immunoreactivity in both rat and human spinal cord injury suggested a role for neurogenic inflammation in this form of CNS injury (64, 65). Finally, activation of the multimodal TRPV1 receptor that is linked to SP release initiates neurogenic inflammation and is associated with increased BBB permeability, an effect abolished by the TRPV1 antagonist capsazepine and by an NK1 antagonist (66).…”