scholarly journals Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige Smith ◽  
Natalia Ogrodnik ◽  
Janani Satkunarajah ◽  
Meaghan A. O’Reilly
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Focused Ultrasound ◽  
Healthy Tissue ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Intense Staining ◽  
Her2 Breast Cancer ◽  
Sprague Dawley Rats ◽  
Blood Spinal Cord Barrier

AbstractExtensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.

scholarly journals Olfactory bulb transplantation in complete spinal cord injury: axonal regeneration and locomotor recovery

2015 ◽  
Vol 14 (1) ◽  
pp. 50-52
Author(s):  
Carlos Abraham Arellanes-Chávez ◽  
Ariana Martínez Bojórquez ◽  
Ernesto Ramos Martínez
Keyword(s):  
Spinal Cord ◽  
Axonal Regeneration ◽  
Sufficient Evidence ◽  
Spinal Cord Regeneration ◽  
Sprague Dawley ◽  
Locomotor Recovery ◽  
Randomized Controlled ◽  
Sprague Dawley Rats ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

OBJECTIVES: To determine whether the intervention in rats is effective in terms of spinal cord regeneration and locomotor recovery, in order to obtain sufficient evidence to apply the therapy in humans. METHODS: a randomized, controlled, experimental, prospective, randomized trial was conducted, with a sample of 15 adult female Sprague-Dawley rats weighing 250 gr. They were divided into three equal groups, and trained for 2 weeks based on Pavlov's classical conditioning method, to strengthen the muscles of the 4 legs, stimulate the rats mentally, and keep them healthy for the surgery. RESULTS: It was observed that implantation of these cells into the site of injury may be beneficial to the process of spinal cord regeneration after spinal trauma, to mediate secretion of neurotrophic and neuroprotective chemokines, and that the OECs have the ability to bridge the repair site and decrease the formation of gliosis, creating a favorable environment for axonal regeneration. CONCLUSION: It is emphasized that the olfactory ensheathing glial cells possess unique regenerative properties; however, it was not until recently that the activity of promoting central nervous system regeneration was recognized.

scholarly journals Genistein Loaded Nanofibers Protect Spinal Cord Tissue Following Experimental Injury in Rats

2018 ◽  
Author(s):  
Mohamed Ismail ◽  
Sara Ibrahim ◽  
Azza Elamir ◽  
Amira M. Elrafei ◽  
Nageh Allam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Spinal Cord ◽  
Drug Delivery System ◽  
Delivery System ◽  
Enhanced Recovery ◽  
Therapeutic Drug ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Cord Injury

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

scholarly journals α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury

2016 ◽  
Vol 311 (5) ◽  
pp. R971-R978 ◽  
Author(s):  
Hirokazu Ishida ◽  
Hiroki Yamauchi ◽  
Hideaki Ito ◽  
Hironobu Akino ◽  
Osamu Yokoyama
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lower Urinary Tract Dysfunction ◽  
Urethral Sphincter ◽  
Sprague Dawley ◽  
External Urethral Sphincter ◽  
Detrusor Sphincter Dyssynergia ◽  
Sphincter Electromyography ◽  
Sprague Dawley Rats ◽  
Cord Injury

Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.

Responses of T2-4 spinal cord neurons to irritation of the lower airways in the rat

1997 ◽  
Vol 273 (3) ◽  
pp. R1147-R1157 ◽  
Author(s):  
T. Hummel ◽  
J. N. Sengupta ◽  
S. T. Meller ◽  
G. F. Gebhart
Keyword(s):  
Spinal Cord ◽  
Afferent Input ◽  
Sprague Dawley ◽  
Spinal Neurons ◽  
Thoracic Spinal Cord ◽  
Spinal Cord Neurons ◽  
Thoracic Spinal ◽  
Balloon Distension ◽  
Sprague Dawley Rats ◽  
Lower Airways

The aim of the study was to investigate the information processing in the thoracic spinal cord (T2-4) after chemical irritation of the lower airways. Experiments were performed in pentobarbital sodium-anesthetized and pancuronium-paralyzed male Sprague-Dawley rats. Balloon distension of the esophagus was used as the search stimulus. Ammonia and smoke were applied by means of a tracheal cannula; they produced excitatory, inhibitory, and biphasic responses in a concentration-related manner (ammonia 39/39; smoke 23/ 39). Inhaled irritant-responsive neurons exhibited a number of similarities that have been described for neurons responding to stimulation of other thoracic viscera. These similarities relate to the distribution of neurons in the deeper laminae of the thoracic spinal cord, the relatively small number of neurons receiving input from the lower airways, the extensive convergent input from the skin and other thoracic viscera, and the pattern of responses. In addition, both stimulus-induced responses and spontaneous activity are subject to modulation from supraspinal sites. On the basis of responses to inhaled irritants after either spinal cord or vagus nerve block/transection, these T2-4 spinal neurons are likely to receive spinal afferent input that is modulated by vagal-brain stem input.

The role of spinal thrombin through protease-activated receptor 1 in hyperalgesia after neural injury

2017 ◽  
Vol 26 (4) ◽  
pp. 532-541 ◽  
Author(s):  
Jenell R. Smith ◽  
Beth A. Winkelstein
Keyword(s):  
Spinal Cord ◽  
Nerve Root ◽  
Thrombin Inhibitor ◽  
Sham Operation ◽  
Spinal Cord Tissue ◽  
Nerve Root Compression ◽  
Protease Activated Receptor 1 ◽  
Blood Spinal Cord Barrier ◽  
Enzymatic Product

OBJECTIVE Painful neuropathic injuries induce blood–spinal cord barrier (BSCB) breakdown, allowing pro-inflammatory serum molecules to cross the BSCB, which contributes to nociception. The goal of these studies was to determine whether the blood-borne serine protease thrombin also crosses a permeable BSCB, contributing to nociception through its activation of protease-activated receptor-1 (PAR1). METHODS A 15-minute C-7 nerve root compression, which induces BSCB breakdown and painful behaviors by Day 1, was administered in the rat (n = 10); sham operation (n = 11) and a 3-minute compression (n = 10) that does not induce sensitivity were administered as controls. At Day 1 after root compression, spinal cord tissue was co-immunolabeled for fibrin/fibrinogen, the enzymatic product of thrombin, and IgG, a serum protein, to determine whether thrombin acts in areas of BSCB breakdown. To determine whether spinal thrombin and PAR1 contribute to hyperalgesia after compression, the thrombin inhibitor hirudin and the PAR1 antagonist SCH79797, were separately administered intrathecally before compression injuries (n = 5–7 per group). Rat thrombin was also administered intrathecally with and without SCH79797 (n = 6 per group) to determine whether spinal thrombin induces hypersensitivity in naïve rats through PAR1. RESULTS Spinal fibrin(ogen) was elevated at Day 1 after root compression in regions localized to BSCB breakdown and decreased in those regions by Day 7. Blocking either spinal thrombin or PAR1 completely prevented compression-induced hyperalgesia for 7 days. Intrathecal thrombin induced transient pain that was prevented by blocking spinal PAR1 before its injection. CONCLUSIONS The findings of this study suggest a potent role for spinal thrombin and its activation of PAR1 in pain onset following neuropathic injury.

Biocompatibility and biodegradability of implantable drug delivery matrices based on novel poly(decane-co-tricarballylate) photocured elastomers

2012 ◽  
Vol 27 (1) ◽  
pp. 78-94 ◽  
Author(s):  
Mohamed A. Shaker ◽  
Noriko Daneshtalab ◽  
Jules J.E. Doré ◽  
Husam M. Younes
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Degradation Products ◽  
Mitochondrial Activity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Diphenyltetrazolium Bromide ◽  
Tissue Reactions

Visible light photo-cross-linked biodegradable amorphous elastomers based on poly(decane- co-tricarballylate) (PDET) with different cross-linking densities were synthesized, and their cytotoxicity, biocompatibility, and biodegradability were reported. Cytotoxicity of PDET extracts of the elastomers was assessed for mitochondrial succinate dehydrogenase activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and inhibition of [3H] thymidine incorporation into DNA of epithelial cells. The in vivo biocompatibility and biodegradability were determined by subcutaneous implantation of PDET microcylinders in 25 male Sprague–Dawley rats over a period of 12 weeks. The in vivo changes in physical and mechanical parameters of the implants were compared with those observed in vitro. The treated epithelial cells revealed no signs of cytotoxicity, and the elastomer degradation products caused only a slight stimulation to both mitochondrial activity and DNA replication. The implants did not exhibit any macroscopic signs of inflammation or adverse tissue reactions at implant retrieval sites. The retrieved implanted microcylinders maintained their original geometry and extensibility in a manner similar to those observed in vitro. These new elastomers have excellent biocompatibility and are considered promising biomaterials for controlled drug delivery and tissue engineering applications.

scholarly journals Pregabalin alleviates postherpetic neuralgia by downregulating spinal TRPV1 channel protein

2021 ◽  
Vol 20 (11) ◽  
pp. 2287-2292
Author(s):  
Zhenping Xiao ◽  
Mengjun Liao ◽  
Yunwu He ◽  
Yonglin Li ◽  
Wuzhou Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Postherpetic Neuralgia ◽  
New Drugs ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Trpv1 Channel ◽  
Channel Protein ◽  
Tnf Α ◽  
Prefrontal Lobe

Purpose: To determine the mechanism involved in pregabalin-induced alleviation of postherpetic neuralgia in a rat model.Methods: Ninety-sixty healthy Sprague-Dawley (SD) rats were assigned to sham, model andpregabalin groups (32 rats per group). A model of postherpetic neuralgia (PN) was established. The expressions of IL-1β and TNF-α in spinal cord tissue were determined 7 days after administration of treatments. The proportions of fluorescence areas in astrocytes in the dorsal horn, prefrontal lobe and hippocampus, and level of spinal cord TRPV1 channel protein in each group were evaluated.Results: Relative to model rats, IL-1β and TNF-α in spinal cord of pregabalin rats were significantly reduced (p < 0.05). The areas of fluorescence in astrocytes in dorsal horn of spinal cord, prefrontal lobe and hippocampus of model group were significantly increased, relative to sham, but were decreased in rats in pregabalin group (p < 0.05).Conclusion: Pregabalin significantly alleviates postherpetic neuralgia via mechanisms which may be related to the inflammatory response of spinal dorsal horn and downregulation of TRPV1 channel protein expression. This finding may be useful in developing new drugs for alleviating postherpetic neuralgia.

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