Browsing by Subject "Peripheral nerve injury"

Now showing 1 - 3 of 3
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    Biohacking Nerve Repair: Novel Biomaterials, Local Drug Delivery, Electrical Stimulation, and Allografts to Aid Surgical Repair
    (MDPI, 2024-07-31) Crabtree, Jordan R.; Mulenga, Chilando M.; Tran, Khoa; Feinberg, Konstantin; Santerre, J. Paul; Borschel, Gregory H.; Surgery, School of Medicine
    The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination.
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    Mesenchymal stem cells and local tacrolimus delivery synergistically enhance neurite extension
    (Wiley, 2021) Saffari, Sara; Saffari, Tiam M.; Chan, Katelyn; Borschel, Gregory H.; Shin, Alexander Y.; Surgery, School of Medicine
    Background: The aim of this study was to investigate the combined effect of mesenchymal stem cells (MSC) and local delivery of tacrolimus (FK506) on nerve regeneration when applied to nerve autografts and decellularized allografts. Methods: A three-dimensional in vitro compartmented cell culture system consisting of a neonatal dorsal root ganglion adjacent to a nerve graft was used to evaluate the regenerating neurites into the peripheral nerve scaffold. Nerve autografts and allografts were treated with (i) undifferentiated MSCs, (ii) FK506 (100 ng/mL) or (iii) both (N = 9/group). After 48 hours, neurite extension was measured to quantify nerve regeneration and stem cell viability was evaluated. Results: Stem cell viability was confirmed in all MSC-treated grafts. Neurite extension was superior in autografts treated with FK506, and MSCs and FK506 combined (p < 0.001 and p = 0.0001, respectively), and autografts treated with MSCs (p = 0.12) were comparable to untreated autografts. In allografts, FK506 treatment and combined treatment were superior to controls (p < 0.001 and p = 0.0001, respectively), and treatment with MSCs (p = 0.09) was comparable to controls. All autograft groups were superior compared to their respective allograft treatment group (p < 0.05) in neurite extension. Conclusions: Alone, either MSC or FK506 treatment improved neurite outgrowth, and combined they further enhanced neurite extension in both autografts and allografts.
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    Peripheral nerve injury reduces the excitation-inhibition balance of basolateral amygdala inputs to prelimbic pyramidal neurons projecting to the periaqueductal gray
    (BMC, 2020-06-29) Cheriyan, John; Sheets, Patrick L.; Pharmacology and Toxicology, School of Medicine
    Cellular and synaptic mechanisms underlying how chronic pain induces maladaptive alterations to local circuits in the medial prefrontal cortex (mPFC), while emerging, remain unresolved. Consistent evidence shows that chronic pain attenuates activity in the prelimbic (PL) cortex, a mPFC subregion. This reduced activity is thought to be driven by increased inhibitory tone within PL circuits. Enhanced input from the basolateral amygdala (BLA) to inhibitory neurons in PL cortex is one well-received mechanism for this circuit change. In mice, we used retrograde labeling, brain slice recordings, and optogenetics to selectively stimulate and record ascending BLA inputs onto PL neurons that send projections to the periaqueductal gray (PAG), which is a midbrain structure that plays a significant role in endogenous analgesia. Activating BLA projections evoked both excitatory and inhibitory currents in cortico-PAG (CP) neurons, as we have shown previously. We measured changes to the ratio of BLA-evoked excitatory to inhibitory currents in the spared nerve injury (SNI) model of neuropathic pain. Our analysis reveals a reduced excitation-inhibition (E/I) ratio of BLA inputs to PL-CP neurons 7 days after SNI. The E/I ratio of BLA inputs to CP neurons in neighboring infralimbic (IL) cortex was unchanged in SNI animals. Collectively, this study reveals that the overall E/I balance of BLA inputs to PL neurons projecting to the PAG is reduced in a robust neuropathic pain model. Overall, our findings provide new mechanistic insight into how nerve injury produces dysfunction in PL circuits connected to structures involved in pain modulation.