The Influence of Brain Injury or Peripheral Nerve Injury on Calcitonin Gene-Related Peptide Concentration Variation and Fractures Healing Process

Abstract

To investigate the changes of calcitonin gene-related peptide (CGRP) in rat's blood plasma, spinal anterior motorneuron, and dorsal root ganglion (DRG) after fractures combined with central or peripheral nerve injuries and its influence on fracture healing, 72 healthy adult SD rats (male or female) were divided into 4 groups (18 rats in each group): group A, simple(left) tibial fracture; group B, left tibial fracture combined with left sciatic nerve injury; group C, left tibial fracture combined with T9-11 spinal cord transection injury; group D, left tibial fracture combined with right cerebral cortex injury. Group A was the control group. The concentration of serum CGRP was measured immediately, 1w, 2w, and 4w after injury using radio immunoassay. X-ray photograph was taken at 1w, 2w, and 4w after injury to assess fracture healing. The concentration of serum CGRP in spinal anterior motorneuron and dorsal root ganglion was measured 1w, 2w, and 4w after injury. Bony callus at 2w after injury using H.E.staining was observed. 1w and 2w after injury, the fracture line was still clear on the X-ray of all groups, but 4w after injury the fracture line disappeared with complete healing except the peripheral nerve injury group. By H.E. staining, we found lesser bony callus contents in the peripheral nerve injury group than the simple fracture group at 2w after injury; irregular bone trabecula and healing defect were found in the former group. While the spinal injury group and cerebral cortex injury group represented more bony callus than the simple fracture group, increased bone trabecula and regularity, medullary cavity occluded and finally solid bony connections were found. CGRP concentration in blood plasma and spinal anterior motorneuron represented no apparent differences among all groups during each observation period. For the dorsal root ganglion group, 1w after fracture, there was no apparent difference of CGRP concentration in the peripheral nerve injury group and cerebral cortex group compared with the control group (P > 0.05), but the spinal injury group showed more CGRP than the control group (P < 0.01). 2w after injury, the peripheral nerve injury group and cerebral cortex group also showed no difference compared with the control group, but the cerebral cortex group had more CGRP contents than the peripheral nerve injury group (P < 0.05), and the spinal injury group showed more CGRP than the control group (P < 0.01). 4w after injury, the peripheral nerve group, spinal injury group, and cerebral cortex injury group all showed higher concentration of CGRP than the control group. Among the 3 groups, the spinal injury group is the highest (P < 0.01). When fracture combined with peripheral nerve injury, the healing process can be slowed down. In contrast, fracture combined with spinal injury and cerebral cortex injury will accelerate the healing process. The CGRP in dorsal root ganglion in spinal injury group and cerebral cortex injury group increased, which may have positive effects on fracture healing.

NPY and CGRP Inhibitor Influence on ERK Pathway and Macrophage Aggregation during Fracture Healing

“…This finding shed some light upon the process by which CGRP influences fracture recovery. Consistently, another research study had a similar result when a bone fracture combined with cerebral cortex injury demonstrated a faster healing process [14]. Although in our study we did not deeply investigate the relationship between brain injury and fracture healing, we discerned the high levels of NPY and CGRP during healing process in the injured areas, indicating a potential relationship between these two types of neurotransmitters and fracture healing.…”

“…Li et al found that CGRP had a positive effect on mineralization and remodeling of bone by regulating NOS [13]. Zhang et al claimed that CGRP participated in bone metabolism and promoted swifter fracture healing [14]. Moreover, in a recent study, Tian et al confirmed that CGRP promoted osteogenic differentiation as well as proliferation [15].…”

Effects of Treatment of Treadmill Combined with Electro-Acupuncture on Tibia Bone Mass and Substance PExpression of Rabbits with Sciatic Nerve Injury

“…The peripheral nervous system may play an important role in bone healing following fracture or other trauma [4–6]. Bone fractures accompanied by peripheral nerve injuries heal slower [7] and sensory denervation negatively affects long-term prognosis[8]. Substance P (SP), a neuropeptide belonging to the tachykinin family, is widely distributed in the body, particularly in the central and peripheral nervous systems where it acts as a neurotransmitter or neuromodulator [9].…”

“…Previous studies focused primarily on the damaged peripheral nerves themselves and denervated muscle [18,19]. Although bone healing combined with peripheral nerve injury has been investigated [4,5,7,8], interventions for denervated bones have not been extensively studied. This study measures the effects of combining treadmill running with Jiaji-EA on tibia bone mass, bone strength and SP expression in rabbits with sciatic nerve injury.…”

Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury

“…CGRP plays a well-recognized and pivotal role in repairing tissue, activating its cognate G protein-coupled receptor to initiate intracellular signaling2223. Following tissue injury, such as SCI, increased CGRP participates in vasodilation, sensory transmission, immune modulation and nerve regeneration2425262728. Recently, MSCs were found to express CGRP receptors on the cell membrane surface2930.…”