Magnetic Resonance Imaging as a Biomarker in Rodent Peripheral Nerve Injury Models Reveals an Age-Related Impairment of Nerve Regeneration

Abstract Assessment of myelin integrity in peripheral nerve injuries and pathologies has largely been limited to post-mortem analysis owing to the difficulty in obtaining biopsies without affecting nerve function. This is further encumbered by the small size of the tissue and its location. Therefore, the development of robust, non-invasive methods is highly attractive. In this study, we used magnetic resonance imaging (MRI) techniques, including magnetization transfer ratio (MTR), to longitudinally and non-invasively characterize both the sciatic nerve crush and lysolecithin (LCP) demyelination models of peripheral nerve injury in rodents. Electrophysiological, gene expression and histological assessments complemented the extensive MRI analyses in young and aged animals. In the nerve crush model, MTR analysis indicated a slower recovery in regions distal to the site of injury in aged animals, as well as incomplete recovery at six weeks post-crush when analyzing across the entire nerve surface. Similar regional impairments were also found in the LCP demyelination model. This research underlines the power of MTR for the study of peripheral nerve injury in small tissues such as the sciatic nerve of rodents and contributes new knowledge to the effect of aging on recovery after injury. A particular advantage of the approach is the translational potential to human neuropathies.

Download Full-text

Diffusion Magnetic Resonance Imaging Predicts Peripheral Nerve Recovery in a Rat Sciatic Nerve Injury Model

Plastic & Reconstructive Surgery ◽

10.1097/prs.0000000000006638 ◽

2020 ◽

Vol 145 (4) ◽

pp. 949-956

Author(s):

Angel F. Farinas ◽

Isaac V. Manzanera Esteve ◽

Alonda C. Pollins ◽

Nancy L. Cardwell ◽

Christodoulos Kaoutzanis ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Diffusion Magnetic Resonance Imaging ◽

Resonance Imaging ◽

Rat Sciatic Nerve ◽

Injury Model ◽

Nerve Recovery

Download Full-text

Magnetic Resonance Imaging Signal Changes in Denervated Muscles after Peripheral Nerve Injury

Neurosurgery ◽

10.1097/00006123-199412000-00010 ◽

1994 ◽

Vol 35 (6) ◽

pp. 1077???1086 ◽

Cited By ~ 4

Author(s):

G. Alexander West ◽

David R. Haynor ◽

Robert Goodkin ◽

Jay S. Tsuruda ◽

Andrew D. Bronstein ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Signal ◽

Signal Changes ◽

Denervated Muscles

Download Full-text

Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

Neural Plasticity ◽

10.1155/2014/786985 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11

Author(s):

Liang Shu ◽

Jingjing Su ◽

Lingyan Jing ◽

Ying Huang ◽

Yu Di ◽

...

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Recurrent Inhibition ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Nerve Crush Injury

Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.

Download Full-text

Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02108-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Erin-Mai F. Lim ◽

Vahid Hoghooghi ◽

Kathleen M. Hagen ◽

Kunal Kapoor ◽

Ariana Frederick ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Cytokines And Chemokines ◽

Inflammatory Macrophages ◽

Nerve Crush Injury

Abstract Background Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury. Methods Sciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab−/−) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting. Results We report that (1) more pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab−/− mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro. Conclusions CRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.

Download Full-text