Histomorphometric and ultrastructural evaluation of long term alpha lipoic acid and vitamin b12 use after experimental sciatic nerve injury in rats

AbstractChronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed animals to consume Δ9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Animals stably consumed these gelatins over 3 weeks, with detectable serum levels. We designed a real-time gelatin measurement system, and observed that mice consumed gelatin throughout the light and dark cycles, with THC-gelatin animals consuming less than the other groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after one week while THC or CBD reduced allodynia over three weeks. Hyperalgesia took longer to develop after sciatic nerve injury, but by the last day of testing THC significantly reduced hyperalgesia responses, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by both THC and CBD. This study demonstrates that mice will voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids can provide long-term relief of chronic pain states. Additionally, ultrasonic clicks may objectively represent the pain status of a mouse and could be integrated into future pain models.

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Long-Term Functional Outcome of Penetrating Sciatic Nerve Injury

Journal of Trauma and Acute Care Surgery ◽

10.1097/01.ta.0000245904.54302.a2 ◽

2008 ◽

Vol 64 (3) ◽

pp. 790-795 ◽

Cited By ~ 5

Author(s):

Yoram A. Weil ◽

Andrew D. Pearle ◽

Lampros Palladas ◽

Meir Liebergall ◽

Rami Mosheiff

Keyword(s):

Sciatic Nerve ◽

Functional Outcome ◽

Nerve Injury ◽

Sciatic Nerve Injury

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Micro- and Astroglia Activity in the Spinal Cord Ventrolateral Nucleus Sciatic Nerve Injury in Rats

Cell and Tissue Biology ◽

10.1134/s1990519x20040100 ◽

2020 ◽

Vol 14 (4) ◽

pp. 263-269

Author(s):

A. A. Starinets ◽

E. L. Egorova ◽

A. A. Tyrtyshnaia ◽

I. V. Dyuisen ◽

A. N. Baryshev ◽

...

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Ventrolateral Nucleus

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Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

Clinical Phytoscience ◽

10.1186/s40816-021-00263-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Prasad Neerati ◽

Harika Prathapagiri

Keyword(s):

Neuropathic Pain ◽

Peripheral Neuropathy ◽

Sciatic Nerve ◽

Lipoic Acid ◽

Normal Saline ◽

Chronic Constriction Injury ◽

Thermal Hyperalgesia ◽

Alpha Lipoic Acid ◽

Chronic Neuropathic Pain ◽

Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

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3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02315-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Diego Noé Rodríguez-Sánchez ◽

Giovana Boff Araujo Pinto ◽

Luciana Politti Cartarozzi ◽

Alexandre Leite Rodrigues de Oliveira ◽

Ana Livia Carvalho Bovolato ◽

...

Keyword(s):

Growth Factor ◽

Sciatic Nerve ◽

Nerve Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Sciatic Nerve Injury ◽

Motor Deficits ◽

3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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