312 An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 266-267
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Erin Paschel ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
The Body ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Histopathological Response ◽  
Histological Techniques ◽  
Sensory Deficits ◽  
The Right

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective technique to create lesions of the brain and trigeminal nerve (TGN) in order to achieve neuromodulation. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain sensitivity and can be targeted to treat chronic and debilitating pain in the extremities. Neuromodulation of the DRG might therefore improve chronic peripheral pain. This study was performed to determine the feasibility as well as clinical and histological effects of delivering high dose SRS targeted to the lumbar DRG in a rat model. METHODS Four Sprague Dawley male rats underwent 80 Gy maximum dose single-fraction SRS to the left L5 and L6 DRG using the Leksell Gamma Knife Icon (Elekta, Atlanta, GA) with onboard cone-beam CT imaging using 4 mm diameter collimators. The right L5 and L6 DRGs served as the controls. The animals were evaluated for motor and sensory deficits every two weeks. Two animals were sacrificed at 3 and two at 6 months after SRS. The lumbar spines were harvested and decalcified. Common histological techniques (Masson trichrome, Prussian blue) were used to assess for fibrosis and demyelination. RESULTS >No detectable motor or sensory deficits were seen in any animal. Histological changes including fibrosis and loss of myelin were noted to the left L5 and L6 DRGs, but not the right side control DRGs. Fibrotic changes within the vertebral body were also evident on the treated sides of the vertebral bodies. CONCLUSION We were able to detect a demyelinating histopathological response from SRS delivered to the DRG in rats. Since such changes mimic those seen after trigeminal SRS in experimental animals, we hypothesize that radiosurgery may be a potential option in chronic spinal radicular pain amenable to neuromodulation.

scholarly journals Radiosurgery to the Spinal Dorsal Root Ganglion Induces Fibrosis and Inhibits Peripheral Glial Cell Activation While Preserving Axonal Neurotransmission

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
L Dade Lunsford ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Cell Activation ◽  
The Body ◽  
Male Rats ◽  
Gasserian Ganglion ◽  
Sprague Dawley ◽  
Spinothalamic Tract ◽  
Satellite Glial Cells ◽  
Sensory Deficits

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is an effective technique to create lesions in the trigeminal nerve to treat trigeminal neuralgia. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain. Therefore, SRS to the DRG might improve radiculopathic pain. This study was performed to examine the functional and structural effects of 40 or 80 Gy to the DRG in a rat model. METHODS A total of 8 Sprague Dawley male rats underwent 40 or 80 Gy single fraction SRS to the left L5 and L6 DRGs using the Leksell Gamma Knife Icon. The contralateral DRG served as controls. Animals were sacrificed after 3 mo, and the spines were harvested. Common histology was used to assess fibrosis and inflammation. DRGs were stained for Glial Fibrillar Acidic Protein (GFAP) and Neu-N as a measure of peripheral glial activation and neurogenesis respectively. The Von Frey Test was used to assess the integrity of the spinothalamic tract. Animals were evaluated for motor and sensory deficits bi-weekly. RESULTS No motor or sensory deficits resulted from SRS in any animal. Histological changes including fibrosis, edema, and vascular sclerosis were present on the treated, but not the control side and were more pronounced at the higher dose. SRS reduced the expression of GFAP without affecting the expression of Neu-N or internexin. The Von Frey Test did not show any differences between the two sides at either dose. CONCLUSION Both doses were well tolerated and provoked no deficits, neuronal lysis, or altered the function of spinothalamic axons. SRS reduced the activation of satellite glial cells, a primary mechanism for DRG mediated pain, and elicited similar changes as the ones described to the Gasserian ganglion after SRS signaling that SRS might be effective for the treatment of refractory radiculopathic pain.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

scholarly journals Radiosurgery to the spinal dorsal root ganglion induces fibrosis and inhibits satellite glial cell activation while preserving axonal neurotransmission

2020 ◽  
Vol 32 (6) ◽  
pp. 790-798 ◽  
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Rachel Wolfe ◽  
Ajay Niranjan ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Substance P ◽  
Dorsal Root Ganglion ◽  
Trigeminal Neuralgia ◽  
Dorsal Root ◽  
High Dose ◽  
Gasserian Ganglion ◽  
Spinothalamic Tract ◽  
Satellite Glial Cells ◽  
Control Side

OBJECTIVEStereotactic radiosurgery (SRS) has been used to treat trigeminal neuralgia by targeting the cisternal segment of the trigeminal nerve, which in turn triggers changes in the gasserian ganglion. In the lumbar spine, the dorsal root ganglion (DRG) is responsible for transmitting pain sensitivity and is involved in the pathogenesis of peripheral neuropathic pain. Therefore, radiosurgery to the DRG might improve chronic peripheral pain. This study evaluated the clinical and histological effects of high-dose radiosurgery to the DRG in a rodent model.METHODSEight Sprague-Dawley rats received either 40- or 80-Gy SRS to the fifth and sixth lumbar DRGs using the Leksell Gamma Knife Icon. Animals were euthanized 3 months after treatment, and the lumbar spine was dissected and taken for analysis. Simple histology was used to assess collagen deposition and inflammatory response. GFAP, Neu-N, substance P, and internexin were used as a measure of peripheral glial activation, neurogenesis, pain-specific neurotransmission, and neurotransmission in general, respectively. The integrity of the spinothalamic tract was assessed by means of the von Frey test.RESULTSThe animals did not exhibit any signs of motor or sensory deficits during the experimentation period. Edema, fibrosis, and vascular sclerotic changes were present on the treated, but not the control, side. SRS reduced the expression of GFAP without affecting the expression of Neu-N, substance P, or internexin. The von Frey sensory perception elicited equivalent results for the control side and both radiosurgical doses.CONCLUSIONSSRS did not alter sensory or motor function but reduced the activation of satellite glial cells, a pathway for DRG-mediated pain perpetuation. Radiosurgery provoked changes equivalent to the effects of focal radiation on the trigeminal ganglion after SRS for trigeminal neuralgia, suggesting that radiosurgery could be successful in relieving radiculopathic pain.

Histopathological Changes of Organs (Lungs, Liver, Kidney, and Brain) After Using Two Types of AgiCoat and Acticoat Nanosilver Dressings on Deep Second-Degree Burn in Rat

2019 ◽  
Vol 41 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hamid Karimi ◽  
Noor-Ahmad Latifi ◽  
Ali Zare Mehrjerdi ◽  
Babak Jafarnejad ◽  
Ali-Mohammad Karimi
Keyword(s):  
Wound Healing ◽  
Silver Ions ◽  
The Body ◽  
Male Rats ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Degree Burn ◽  
Significant Difference ◽  
Second Degree

Abstract Prevention of infections is a very important issue in treating the burn wounds. The nanosilver dressings have many promising advantages, but absorption of silver ions and its adverse effects to the body were always a question. The aim of this study was to compare Silver serum levels and acute toxic effects of nanosilver on histopathology of organs (lungs, liver, kidney, spleen, and brain) in two types of AgiCoat and Acticoat (nanosilver) dressings on second-degree deep burn in rat. This is an experimental study conducted in our animal laboratory. We divided 24 Sprague–Dawley male rats weighing 300 to 350 randomly into two groups. After anesthesia, a second deep-degree burn was made over dorsal skins of rats by standard method. For group A, Agicoat and, for group B, Acticoat dressings were used. The dressings were changed every 3 days with AgiCoat and Acticoat, respectively. After 14 days, we got blood samples and tissue samples taken from heart, liver, kidneys, spleen, lungs, and brain and a sample from dorsal skin of the rat for histopathological examinations. The results showed that the levels of serum silver in both groups were significantly higher than the standard level (1.22 part per million (PM); AgiCoat, P = .017; Acticoat, P = .000), but there was no significant difference between the groups (P = .551). Examination of the relationship between the level of serum silver and histopathological changes in liver showed that hepatotoxicity of AgiCoat was higher compared with Acticoat and the difference was significant (P = .002). There were no pathological changes in brain, kidneys, spleen, heart, and lungs. Wound healing was faster in Acticoat group. The nanosilver dressings can cause toxicity in liver but not in kidney, brain, spleen, heart, and lungs. Liver pathology and hepatotoxicity were more prominent in AgiCoat group. Wound healing was faster in Acticoat group.

scholarly journals Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abdulsamad Alsalahi ◽  
Mahmood Ameen Abdulla ◽  
Mohammed Al-Mamary ◽  
Mohamed Ibrahim Noordin ◽  
Siddig Ibrahim Abdelwahab ◽  
...  
Keyword(s):  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Catha Edulis ◽  
Male And Female ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Serum Aspartate Aminotransferase ◽  
Liver And Kidney ◽  
Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 101-118 ◽  
Author(s):  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Food Consumption ◽  
Water Intake ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Organ Weights

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100,300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses ≤300 mg/kg or in females at any of the doses tested (≤1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

Exposure of the Dorsal Root Ganglion in Rats to Pulsed Radiofrequency Currents Activates Dorsal Horn Lamina I and II Neurons

Neurosurgery ◽  
2002 ◽  
Vol 50 (4) ◽  
pp. 850-856 ◽  
Author(s):  
Yoshinori Higuchi ◽  
Blaine S. Nashold ◽  
Menno Sluijter ◽  
Eric Cosman ◽  
Robert D. Pearlstein
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Spinal Pain ◽  
Pulsed Radiofrequency ◽  
Sprague Dawley ◽  
Current Electrode ◽  
Spinal Cord Neurons ◽  
Dorsal Ganglion ◽  
Pulsed Rf

Abstract OBJECTIVE: Application of pulsed radiofrequency (RF) currents to the dorsal ganglion has been reported to produce long-term relief of spinal pain without causing thermal ablation. The present study was undertaken to identify spinal cord neurons activated by exposure of the dorsal ganglion to pulsed RF currents in rats. METHODS: Left-sided hemilaminectomy was performed in adult Sprague-Dawley rats to expose the C6 dorsal root ganglion. An RF electrode (0.5 mm diameter) with a thermocouple for temperature monitoring was positioned on the exposed ganglion, and rats were assigned to one of three treatment groups: pulsed RF treatment (20 ms of 500-kHz RF pulses delivered at a rate of 2 Hz for 120 s to produce tissue heated to 38°C), continuous RF (continuous RF currents for 120 s to produce tissue heated to 38°C), or sham treatment (no RF current; electrode maintained in contact with ganglion for 120 s). RESULTS: Treatment with pulsed RF but not continuous RF was associated with a significant increase in the number of cFOS-immunoreactive neurons in the superficial laminae of the dorsal horn as observed 3 hours after treatment. CONCLUSION: Exposure of the dorsal ganglion to pulsed RF currents activates pain-processing neurons in the dorsal horn. This effect is not mediated by tissue heating.

Noxious Lingual Stimulation Influences the Excitability of the Face Primary Motor Cerebral Cortex (Face MI) in the Rat

2008 ◽  
Vol 100 (3) ◽  
pp. 1234-1244 ◽  
Author(s):  
K. Adachi ◽  
G. M. Murray ◽  
J.-C. Lee ◽  
B. J. Sessle
Keyword(s):  
Cerebral Cortex ◽  
Isotonic Saline ◽  
Internal Capsule ◽  
Male Rats ◽  
Hypoglossal Nucleus ◽  
Emg Activity ◽  
Noxious Stimulation ◽  
Sprague Dawley ◽  
Orofacial Region ◽  
The Right

The mechanisms whereby orofacial pain affects motor function are poorly understood. The aims were to determine whether 1) lingual algesic chemical stimulation affected face primary motor cerebral cortex (face MI) excitability defined by intracortical microstimulation (ICMS); and 2) any such effects were limited to the motor efferent MI zones driving muscles in the vicinity of the noxious stimulus. Ketamine-anesthetized Sprague–Dawley male rats were implanted with electromyographic (EMG) electrodes into anterior digastric, masseter, and genioglossus muscles. In 38 rats, three microelectrodes were located in left face MI at ICMS-defined sites for evoking digastric and/or genioglossus responses. ICMS thresholds for evoking EMG activity from each site were determined every 15 min for 1 h, then the right anterior tongue was infused (20 μl, 120 μl/h) with glutamate (1.0 M, n = 18) or isotonic saline ( n = 7). Subsequently, ICMS thresholds were determined every 15 min for 4 h. In intact control rats ( n = 13), ICMS thresholds were recorded over 5 h. Only left and right genioglossus ICMS thresholds were significantly increased (≤350%) in the glutamate infusion group compared with intact and isotonic saline groups ( P < 0.05). These dramatic effects of glutamate on ICMS-evoked genioglossus activity contrast with its weak effects only on right genioglossus activity evoked from the internal capsule or hypoglossal nucleus. This is the first documentation that intraoral noxious stimulation results in prolonged neuroplastic changes manifested as a decrease in face MI excitability. These changes appear to occur predominantly in those parts of face MI that provide motor output to the orofacial region receiving the noxious stimulation.

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