scholarly journals Amitriptyline Accelerates SERT Binding Recovery Rate in MDMA-Induced Rat Model: In Vivo 4-[18F]-ADAM PET Imaging

2021 ◽  
Author(s):  
Skye Hsin-Hsien Yeh ◽  
Chuang-Hsin Chiu ◽  
Yu-Yeh Kuo ◽  
Chi-Jung Tsai ◽  
Tsung-Hsun Yu ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Rat Model ◽  
Recovery Rate ◽  
Neuroprotective Effect ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Fiber Density ◽  
Neuroprotective Effects ◽  
Immunochemical Staining

Abstract Background Numerous studies have confirmed that 3, 4-Methylenedioxymethamphetamine (MDMA) produces long-lasting changes to the serotonergic system and decreases the density of the serotonin reuptake transporter (SERT). However, amitriptyline (AMI) is a potent neuroprotector that can cause devastating neuropathologic injury. Use of 4-[18F]-ADAM, a SERT-specific radionuclide as a molecular imaging agent, facilitates longitudinal, non-invasive assessment of SERT activity/expression post-MDMA. We used 4-[18F]-ADAM PET imaging to access the longitudinal alteration of SERT binding and evaluate the synergistic neuroprotective effect of MDMA and SERT inhibition by AMI in rat model.Materials and Methods The adult male Sprague–Dawley (SD) rats are grouped into four according to drug administration (Group 1: saline, Group 2: MDMA 10mg/kg i.p., Group 3: MDMA 10mg/kg i.p. with AMI 5 mg/kg i.p., Group 4: AMI 5 mg/kg i.p.). All drugs were administrated twice daily for 4 successive days (Day 1 to Day 4). Post-drug 4-[18F]-ADAM PET scans were performed on day 14, day 21 and day 28 to measure the SERT occupancy/recovery. After the last PET imaging, SERT-positive cells were measured quantitatively using immunochemical staining.Results In response to MDMA treatment regimens, SERT binding was significantly reduced in rat brain. Recovery rate (normalized to baseline) in the MDMA group, at day 14 was 64.34% ± 2.05%, progressively increased to 70.70% ± 3.96% at day 28. Recovery rate in the MDMA group varies based on region-specific. AMI dramatically increased SERT binding in all brain regions, enhancing average ~24% recovery rate at day 14 when compared with the MDMA group (MDMA 64.34% ± 2.05% vs. MDMA+ AMI 87.76% ± 2.98%), reaching 84.38% ± 2.05% at day 28. The immunochemical staining revealed that MDMA treatment reduced SERT immunoactivity densities in all brain regions, whereas AMI markedly increased the serotonergic fiber density after MDMA-induction that confirmed the PET findings.Conclusions Using in vivo longitudinal PET imaging, we demonstrated that SERT recovery was positively correlated with the duration of MDMA abstinence, implying the lower SERT densities in MDMA-induced rats reflected neurotoxic effects, varied region-specific, and reversible. AMI globally accelerated the recovery rate of SERT binding and increased SERT fiber density with possible neuroprotective effects.

Abstract 173: The Neuroprotective Effect Of JZL184 is Comparable With Therapeutic Hypothermia in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Jennifer Bradley ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Rat Model ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Flow Index ◽  
Protective Effects ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p < 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p<0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p <0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of cardiac arrest.

scholarly journals Effects of GLP-1 Receptor Activation on a Pentylenetetrazole—Kindling Rat Model

2019 ◽  
Vol 9 (5) ◽  
pp. 108 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Mohamed Eldosoky ◽  
Mohamed El-Shafey ◽  
Mohamed El-Mesery ◽  
Khaled M. Abbas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Ptz Kindling ◽  
Markers Of Oxidative Stress ◽  
Brain Tissues

Objectives: To study the possible anti-seizure and neuroprotective effect of glucagon like peptide 1 (GLP1) analogue (liraglutide) in a pentylenetetrazole (PTZ) induced kindled rat model and its underlying mechanisms. Methods: Thirty Sprague Dawley rats were allocated into 3 equal groups; i) Normal group: normal rats received normal saline, ii) PTZ (kindling) group: received PTZ (50 mg/Kg intraperitoneally (i.p.)) every other day for 2 weeks and iii) PTZ + GLP1 group: same as the PTZ group but rats received liraglutide (75 µg/kg i.p. daily) for 2 weeks before PTZ injection. Seizure severity score, seizure latency and duration were assessed. Also, the expression of caspase-3 (apoptotic marker) and β-catenin (Wnt pathway) by western blotting, markers of oxidative stress (GSH, CAT and MDA) by biochemical assay and the expression of LC3 (marker of autophagy) and heat shock protein 70 (Hsp70) by immunostaining were assessed in hippocampal regions of brain tissues. Results: PTZ caused a significant increase in Racine score and seizure duration with a significant decrease in seizure latency. These effects were associated with a significant increase in MDA, β-catenin, caspase-3, Hsp70 and LC3 in brain tissues (p < 0.05). Meanwhile, liraglutide treatment caused significant attenuation in PTZ-induced seizures, which were associated with significant improvement in markers of oxidative stress, reduction in LC3, caspase-3 and β-catenin and marked increase in Hsp70 in hippocampal regions (p < 0.05). Conclusion: Activation of GLP1R might have anticonvulsant and neuroprotective effects against PTZ-induced epilepsy. These effects could be due to suppression of oxidative stress, apoptosis and autophagy and upregulation of Hsp70.

Neuroprotective effects of erythropoietin on acute metabolic and pathological changes in experimentally induced neurotrauma

2008 ◽  
Vol 109 (4) ◽  
pp. 708-714 ◽  
Author(s):  
Chad E. Hartley ◽  
Madhu Varma ◽  
John P. Fischer ◽  
Richard Riccardi ◽  
Judith A. Strauss ◽  
...  
Keyword(s):  
Parietal Lobe ◽  
Neuroprotective Effect ◽  
Energy Requirement ◽  
Lesion Volume ◽  
Pathological Changes ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Molecular Events ◽  
Extracellular Glucose

Object Head trauma is a dynamic process characterized by a cascade of metabolic and molecular events. Erythropoietin (EPO) has been shown to have neuroprotective effects in animal models of traumatic brain injury (TBI). Acute in vivo mechanisms and pathological changes associated with EPO following TBI are unknown. In this study the authors compare acute metabolic and pathological changes following TBI with and without systemically administered EPO. Methods Right frontal lobe microdialysis cannulae and right parietal lobe percussion hubs were inserted into 16 Sprague–Dawley rats. After a 4- to 5-day recovery, TBI was induced via a DragonFly fluid-percussion device at 2.5–2.8 atm. Rats were randomized into 2 groups, which received 5000 U/kg EPO or normal saline intraperitoneally 30 minutes after TBI. Microdialysis samples for glucose, lactate, pyruvate, and glutamate were obtained every 25 minutes for 10 hours. Rats were killed, their brains processed for light microscopy, and sections stained with H & E. Results Erythropoietin administered 30 minutes after TBI directly affects acute brain metabolism. Brains treated with EPO maintain higher levels of glucose 4–10 hours after TBI (p < 0.01), lower levels of lactate 6–10 hours after TBI (p < 0.01), and lower levels of pyruvate 7.5–10 hours after TBI (p < 0.01) compared with saline-treated controls. Erythropoietin maintains aerobic metabolism after TBI. Systemic EPO administration reduces acute TBI-induced lesion volume (p < 0.05). Conclusions Following TBI, neuron use initially increases, with subsequent depletion of extracellular glucose, resulting in increased levels of extracellular lactate and pyruvate. This energy requirement can result in cell death due to increased metabolic demands. These data suggest that the neuroprotective effect of EPO may be partially due to improved energy metabolism in the acute phase in this rat model of TBI.

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Neuroprotective Effects of the FGF21 Analogue LY2405319

2021 ◽  
pp. 1-13
Author(s):  
Claire Rühlmann ◽  
David Dannehl ◽  
Marcus Brodtrück ◽  
Andrew C. Adams ◽  
Jan Stenzel ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Fibroblast Growth Factor 21 ◽  
Neuroprotective Effects ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures ◽  
Abca1 Mrna

Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analogue LY2405319 (LY), which has a specificity and potency comparable to FGF21. Methods: The present study investigated the potential neuroprotective effect of LY via PPARγ/apoE/abca1 pathway which is known to degrade amyloid-β (Aβ) plaques by using primary glial cells and hippocampal organotypic brain slice cultures (OBSCs) from 30- and 50-week-old transgenic APPswe/PS1dE9 (tg) mice. By LY treatment of 52-week-old tg mice with advanced Aβ deposition, we further aimed to elaborate the effect of LY on AD pathology in vivo. Results: LY application to primary glial cells caused an upregulation of pparγ, apoE, and abca1 mRNA expression and significantly decreased number and area of Aβ plaques in OBSCs. LY treatment in tg mice increased cerebral [18F] FDG uptake and N-acetylaspartate/creatine ratio indicating enhanced neuronal activity and integrity. Although LY did not reduce the number of Aβ plaques in tg mice, the number of iba1-positive cells was significantly decreased indicating reduced microgliosis. Conclusion: These data identified LY in vitro as an activator of Aβ degrading genes leading to cerebral Aβ load amelioration in early and late AD pathology. Although Aβ plaque reduction by LY failed in vivo, LY may be used as therapeutic agent to treat AD-related neuroinflammation and impaired neuronal integrity.

scholarly journals Increased extracellular fluid is associated with white matter fiber degeneration in CADASIL: in vivo evidence from diffusion magnetic resonance imaging

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Yu ◽  
Xinzhen Yin ◽  
Hui Hong ◽  
Shuyue Wang ◽  
Yeerfan Jiaerken ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Extracellular Fluid ◽  
Free Water ◽  
Inverse Correlation ◽  
Brain Regions ◽  
Fiber Density ◽  
Four Levels

Abstract Background White matter hyperintensities (WMHs) are one of the hallmarks of cerebral small vessel disease (CSVD), but the pathological mechanisms underlying WMHs remain unclear. Recent studies suggest that extracellular fluid (ECF) is increased in brain regions with WMHs. It has been hypothesized that ECF accumulation may have detrimental effects on white matter microstructure. To test this hypothesis, we used cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) as a unique CSVD model to investigate the relationships between ECF and fiber microstructural changes in WMHs. Methods Thirty-eight CADASIL patients underwent 3.0 T MRI with multi-model sequences. Parameters of free water (FW) and apparent fiber density (AFD) obtained from diffusion-weighted imaging (b = 0 and 1000 s/mm2) were respectively used to quantify the ECF and fiber density. WMHs were split into four subregions with four levels of FW using quartiles (FWq1 to FWq4) for each participant. We analyzed the relationships between FW and AFD in each subregion of WMHs. Additionally, we tested whether FW of WMHs were associated with other accompanied CSVD imaging markers including lacunes and microbleeds. Results We found an inverse correlation between FW and AFD in WMHs. Subregions of WMHs with high-level of FW (FWq3 and FWq4) were accompanied with decreased AFD and with changes in FW-corrected diffusion tensor imaging parameters. Furthermore, FW was also independently associated with lacunes and microbleeds. Conclusions Our study demonstrated that increased ECF was associated with WM degeneration and the occurrence of lacunes and microbleeds, providing important new insights into the role of ECF in CADASIL pathology. Improving ECF drainage might become a therapeutic strategy in future.

scholarly journals Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sher-Wei Lim ◽  
Hui-Chen Su ◽  
Tee-Tau Eric Nyam ◽  
Chung-Ching Chio ◽  
Jinn-Rung Kuo ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Body Weight Loss ◽  
Motor Dysfunction ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Antibacterial Effects ◽  
Neuroprotective Effects ◽  
Tnf Α

Abstract Background Ceftriaxone is a β-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. Methods Anesthetized male Sprague–Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn’s Gram staining. These parameters above were measured at 72 h after TBI. Results Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. Conclusions The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Neuroprotective Effects of Alisol A 24-acetate on Cerebral Ischemia-reperfusion Injury by Regulating PI3K/AKT Pathway

2021 ◽  
Author(s):  
Taotao Lu ◽  
Huihong Li ◽  
Yangjie Zhou ◽  
Wei Wei ◽  
Linlin Ding ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Brain Regions ◽  
Global Cerebral Ischemia ◽  
Akt Pathway ◽  
Object Recognition Test ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Abstract BackgroundNeuroinflammation and apoptosis are involved in the pathogenesis of ischemic stroke. Alisol A 24-acetate (24A) has a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A in the global cerebral ischemia/ reperfusion (GCI/R) is still unclear. Methods GCI/R mice was used to investigated the neuroprotective effect of 24A. Modified neurological deficit scores, Morris Water Maze and object recognition test were used to evaluate behaviors. The metabolism in brain regions was detected by MRS. The changes of microglia, astrocytes and neurons was detected. The inflammation and apoptosis were measured.Results The results showed that 24A improved behavioral dysfunction and brain metabolism, alleviate neuroinflammation and apoptosis, inhibited microglia and astrocytes activation, which is associated with the activation of PI3K/AKT pathway. ConclusionsTaken together, our study demonstrated that 24A could alleviate GCI/R injury through anti-neuroinflammation and anti-apoptosis via regulating the PI3K/AKT pathway.

Exosome derived from mesenchymal stem cells enhance autophagy and inhibit iNOS/TXNIP/NLRP3 inflammasome axis in injured spinal cord

2020 ◽  
Author(s):  
Bin Lv ◽  
Lei Wang ◽  
Anquan Huang ◽  
Tianming Zou ◽  
Jishan Yuan
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Nlrp3 Inflammasome ◽  
Neuroprotective Effect ◽  
Neuronal Cells ◽  
Tissue Loss ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Cord Injury

Abstract Background: Neuroinflammation, autophagy, NLRP3 inflammasome, and microglia polarizationhave been implicated in spinal cord injury (SCI).Moreover, exosomes, a classic nanovesicles secreted by MSCs, may have a neuroprotective effect on transformation of microglia from the M1 state to the M2 phenotype. However, the effect of MSCs derived exosomes on neuroinflammation is still unclear. Here, we investigated the mechanisms of MSCs derived exosomes mediated NLRP3 inflammasome signaling cascades and its protective effects in SCI. Methods:The SCI model was performed by weight-drop impact in adult male Sprague-Dawley (SD) rats. Control andexosome rats were randomly subjecttoexosomeadminister (20 mg/kg) or placebo via intraperitoneal route 1 h after SCI.Autophagy inhibitor(3-MA) was administered intraperitoneally 20 min before experiment.Neurological function was measured by Basso-Beattie-Bresnahan (BBB) scoring and an open-field test.Neuronal death was measured by HE stainingandNisslstaining.Inducible nitric oxide synthase (iNOS) levels were determined using fluorescent probes. The autophagy and TXNIP and its downstream signaling pathways-mediated polarization of macrophages/microglia was assessed by immunohistochemistry. Results:Exosome significantly downregulated intracellular iNOS and inhibited TXNIP, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation by activating autophagy. Additionally, Exosomepromoted expression of autophagy markers, such as LC3A/B and beclin1,and abrogated the expression of p62. Autophagy inhibitor, 3-MA, blockage of autophagy flux abolished the inhibition of apoptosis and iNOS/TXNIP/NLRP3 inflammasome axisafterSCI. Here, we demonstrated that exosomeadministration in spinal cord markedly reduced tissue loss, attenuate pathological morphology of the injuredregion, and promoted tissue recovery. Moreover. our resultshowed that exosome administration alleviated neuronal cells apoptosis, and inhibited nitric oxide release in microglia.The activation of inflammatoryresponse in neuronal cells facilitates interactions of iNOS‐NLRP3 andTXNIP‐NLRP3and inhibited NLRP3 inflammasome where neuronal cells apoptosis was induced.Further, we found that exosome could suppress macrophages/microglia polarized to M1 phenotype in vivo and in vitro.Taken together, exosome administration exerts protective effects in neuronal cells through inhibiting iNOS production, and exosome administration could inhibit iNOS/TXNIP/NLRP3 inflammasome axis via enhancing autophagy and both in vitro and in vivo. Conclusions:These resultsreveal that exosometreatment alleviatedneuroinflammation and mitigates neuronal apoptosis via autophagy-mediate inhibition of the iNOS/TXNIP/NLRP3 inflammasome axis. Our findings suggest that exosome may be a novel therapeutic target for treating SCI.

Biocompatibility and Efficacy of Five-Channel and Eight-Channel Crosslinked Urethane-Doped Polyester Elastomers (CUPEs) as Nerve Guidance Conduit for Reconstruction of Segmental Peripheral Nerve Defect Using Rat Model

2014 ◽  
Vol 21 ◽  
pp. 57-70
Author(s):  
Angela W.H. Ho ◽  
W.Y. Ip
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Rat Model ◽  
Donor Site ◽  
Nerve Graft ◽  
Nerve Tissue ◽  
Histomorphometric Analysis ◽  
Sprague Dawley ◽  
Fiber Density ◽  
Nerve Guidance Conduit

Introduction: Peripheral nerve injury is common in clinical practice. Nerve defect is a challenging scenario. The current gold standard of managing a nerve defect is autologous nerve graft. However, due to the selection of nerve graft and donor site morbidity, artificial nerve conduits are gaining popularity. However, there are drawbacks of single hollow conduit such as lack of internal support to prevent conduit collapse and inability so as to recreate the proper native spatial arrangement of cells and extracellular matrix within the conduit. In this study, the biocompatibility and efficacy of five-channel and eight-channel Crosslinked Urethane-doped Polyester Elastomers (CUPEs) as nerve guidance conduit will be evaluated through a rat model with reconstruction of segmental peripheral nerve defect. Material and Method: Eighteen adult Sprague-Dawley rats were used. They were randomly allocated to three groups: autograft group, five-channel conduit group and eight-channel conduit group with each consisted of six rats. A 10mm nerve defects were created at the right sciatic nerve. They were bridged with reverse autograft, 5-channel conduit and 8-channel conduit. After eight weeks the rats were euthanized and the reconstructed nerves were harvested for histomorphometric analysis. Result: All conduits showed regenerated nerve tissue inside. There was no collapse of the conduits. There were no severe tissue reaction or scarring near the reconstructed nerve. No neuroma was formed. Histomorphometric analysis showed nerve regeneration was enhanced with increasing number of channels inside conduit. There was overall drop in fiber density between proximal and distal segment among all groups. Conclusion: CUPE nerve guidance conduit is biocompatible and shows good nerve regeneration in reconstructing nerve defect.

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