Abstract To our knowledge, it is the first study which investigates the induction of neuroinflammation in rats by acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception and the astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory response induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by I.M. injection with 100 µL of acidic saline on day 0 and 5, resulted in peripheral sensitization (measured by von-Frey test) and significant (p0.05) increase in IL-1β (160.2±1.1 to 335.2±1.8), IL-6 (100.1±1.4 to 202.4±1.1) and TNF-α (60.0±0.7 to 115.5±1). Light and electron microscopy revealed degenerative changes of the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of GFAP and iNOS. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5µg/kg) i.p attenuated these changes. This trial raises a possibility of dexmedetomidine’s direct effect on astrocytes, peripheral action is also suggested

Abstract To our knowledge, it is the first study which investigates the induction of neuroinflammation in rats by acidic-saline model of fibromyalgia. It is well known that the hippocampus has a fundamental role in pain perception and the astrocytes play a crucial role in pain signaling. Our aim is to evaluate the ability of dexmedetomidine to attenuate the inflammatory response induced in astrocytes. In a group of healthy rats, induction of chronic muscle pain by I.M. injection with 100 µL of acidic saline on day 0 and 5, resulted in peripheral sensitization (measured by von-Frey test) and significant (p0.05) increase in IL-1β (160.2±1.1 to 335.2±1.8), IL-6 (100.1±1.4 to 202.4±1.1) and TNF-α (60.0±0.7 to 115.5±1). Light and electron microscopy revealed degenerative changes of the hippocampus and reactive astrogliosis. Immunohistochemistry showed increased expression of GFAP and iNOS. Surprisingly, treatment with a single dose of an α2-adrenergic agonist, dexmedetomidine (5µg/kg) i.p attenuated these changes. This trial raises a possibility of dexmedetomidine’s direct effect on astrocytes, peripheral action is also suggested

Effective control of postoperative pain is an important concern for both the patient and the physician. Optimization of analgesia with reduction of side effects lead to better outcomes. Unfortunately, this issue remains a challenge. The aim of this study is to determine whether a low dose of systemic magnesium sulfate can synergize the analgesic effect of ketamine in rats and whether this combination can decrease the side effects of ketamine. Adult male Wister rats were assigned into five groups. Group I was kept as normal animals and received no treatment. The surgical animals (incisional pain model was done by a 1-cm planter incision) were divided into four groups (n=10 for each group), group ΙΙ: received saline, group ΙΙΙ: received i.p ketamine 5mg/ kg, group ΙV received s.c. magnesium sulphate 5mg/kg, group V received i.p ketamine 5mg/ kg combined with s.c. magnesium sulphate 5mg/kg. Mechanical hyperalgesia and allodynia were assessed by analgesimeter and von Frey apparatus pre- and post-drug administration. Also, the rotarod apparatus was used to verify the effect of ketamine-magnesium combination on motor impairment. Single administration of ketamine or magnesium sulphate didn’t produce any significant antinociceptive effect. However, significant antinociception was revealed when they were concomitantly administered. Also, this combination didn’t produce any motor impairment. In conclusion, sole administration of ketamine and magnesium sulfate at the assigned doses didn’t inhibit nociception in rats, but their combination produced synergistic antinociception with no sedative effects.

Background: Crhon’s disease (CD) is a multifactorial chronic inflammatory disease that affect the gastrointestinal tract from mouth to anus. The effect of various drugs used to treat CD was investigated. Aim: The aim of the present study is to evaluate the possible therapeutic effect of curcumin on the severity of CD induced by intra-colonic instillation of NaOH in rats. Methods: Adult male Wister rats were assigned into five groups. Group I was kept as normal animals without treatment. Group II, III, IV and V were subjected to the induction of Crhon’s disease by intra-colonic injection of 2ml NaOH (6.25%). Group II received 0.9% saline, group III received dexamethasone at dose of (1mg/kg ), group IV and V received intraperitoneal curcumin (40,100mg/kg) once daily starting 2 days before NaOH infusion until the end of the experiment at day 15 post induction. Assessment of the inflammatory response was done by histology and measurement of interleukin-1β (IL1), tumor necrosis factor (TNF-α), myeloperoxidase activity (MPO) and reduced glutathione (GSH) levels in colon mucosa. Results: High dose of curcumin significantly decreased colonic IL-1β, TNF-α, and MPO activity and increased GSH concentration. Moreover, curcumin attenuated the macroscopic and histopathological changes induced by NaOH. Conclusion: These results suggest that curcumin may be effective in the treatment of CD through its scavenging properties on the oxygen-derived free radicals.

Background: Crhon’s disease (CD) is a multifactorial chronic inflammatory disease that affect the gastrointestinal tract from mouth to anus. The effect of various drugs used to treat CD was investigated. Aim: The aim of the present study is to evaluate the possible therapeutic effect of curcumin on the severity of CD induced by intra-colonic instillation of NaOH in rats. Methods: Adult male Wister rats were assigned into five groups. Group I was kept as normal animals without treatment. Group II, III, IV and V were subjected to the induction of Crhon’s disease by intra-colonic injection of 2ml NaOH (6.25%). Group II received 0.9% saline, group III received dexamethasone at dose of (1mg/kg ), group IV and V received intraperitoneal curcumin (40,100mg/kg) once daily starting 2 days before NaOH infusion until the end of the experiment at day 15 post induction. Assessment of the inflammatory response was done by histology and measurement of interleukin-1β (IL1), tumor necrosis factor (TNF-α), myeloperoxidase activity (MPO) and reduced glutathione (GSH) levels in colon mucosa. Results: High dose of curcumin significantly decreased colonic IL-1β, TNF-α, and MPO activity and increased GSH concentration. Moreover, curcumin attenuated the macroscopic and histopathological changes induced by NaOH. Conclusion: These results suggest that curcumin may be effective in the treatment of CD through its scavenging properties on the oxygen-derived free radicals.

Statins are the most commonly used drugs and the first line treatment for atherosclerotic disorders related to hypercholesterolemia. Myopathy represents the well documented and the most disturbing adverse effects of statins. The underlying mechanism of myopathy is still unknown. The aim of the current study was to evaluate the possible protective role of melatonin in treatment of statin-induced myopathy in rats. Myopathy was determined using biochemical, functional and histopathological examinations. Atorvastatin induced myopathy through prominent muscle wasting and significant increase in serum CK, lactate dehydrogenase and myoglobin levels. Motor activity, evaluated by rotarod test, showed that atorvastatin greatly reduced rats’ motor activity compared to melatonin treated one. We also found that atorvastatin induced ROS generation and increased oxidative stress through evaluation of GSH, MDA, SOD and Nitrite levels. Melatonin significantly attenuated atorvastatin-induced oxidative stress. Ultrastructure examination showed that co-treatment with melatonin reduced degenerative changes and necrosis in gastrocnemius muscle. In conclusion, these results suggest that melatonin has a prominent muscle-protective role in statin-induced myopathy possibly through its antioxidant activity.

Statins are the most commonly used drugs and the first line treatment for atherosclerotic disorders related to hypercholesterolemia. Myopathy represents the well documented and the most disturbing adverse effects of statins. The underlying mechanism of myopathy is still unknown. The aim of the current study was to evaluate the possible protective role of melatonin in treatment of statin-induced myopathy in rats. Myopathy was determined using biochemical, functional and histopathological examinations. Atorvastatin induced myopathy through prominent muscle wasting and significant increase in serum CK, lactate dehydrogenase and myoglobin levels. Motor activity, evaluated by rotarod test, showed that atorvastatin greatly reduced rats’ motor activity compared to melatonin treated one. We also found that atorvastatin induced ROS generation and increased oxidative stress through evaluation of GSH, MDA, SOD and Nitrite levels. Melatonin significantly attenuated atorvastatin-induced oxidative stress. Ultrastructure examination showed that co-treatment with melatonin reduced degenerative changes and necrosis in gastrocnemius muscle. In conclusion, these results suggest that melatonin has a prominent muscle-protective role in statin-induced myopathy possibly through its antioxidant activity.

Background: Pramipexole (PPX), an agonist for Dopamine (DA), has been used to treat both early and advanced Parkinson's Disease (PD). Objectives: This study was done to evaluate the neuroprotective effect of PPX in a DA neuron degeneration model of PD induced by rotenone. Methods: Thirty six male mice were used and divided into three equal groups. The first group, the control group, received only the vehicle (sunflower oil) for a period of 7 weeks (49 days). The second group received rotenone (2mg/kg; IP) dissolved in sunflower oil daily for 49 days. The third group received a combined treatment of rotenone (2mg/kg, IP) and PPX (1mg/kg, IP) daily for 49 days. Behavioral tests were performed a day prior to drug administration and then once weekly along the duration of drugs or vehicle administration. At the end of the 49 days all animals were sacrificed and their midbrains were subjected to immunohistochemical analysis for dopaminergic neurons staining for Anti-Tyrosine Hydroxylase (TH) antibodies. Midbrain tissues were also isolated for biochemical measurements. Results: Behavioral tests revealed that PPX counteracted the rotenone effect in mice locomotor activity and catalepsy. Immunohistochemistry results showed that PPX inhibited the rotenone-induced loss of TH-immunopositive neurons in the substantia nigra pars compacta. Biochemical measurements demonstrated that PPX treatment significantly reversed the rotenone-induced decrease in midbrain DA level. Interestingly, PPX ameliorate the rotenone-induced increase in the malondialdehyde and nitric oxide levels as well as the decrease in total antioxidant capacity. Conclusion: The results indicate the beneficial effect of PPX against the dopaminergic neurodegeneration induced by chronic IP administration of rotenone. This neuroprotective effect seems to be mediated by inhibition of rotenone induced oxidative stress and nitric oxide overproduction and through maintenance of the cellular antioxidant status.

Traumatic Acute Subdural Hematoma: Treatment by Evacuation with Decompressive Craniotomy and Cranioplasty, Case Series and Surgical Outcome Analysis Ahmed.M.Elshanawany1 M.D, Abdelhakeem A. Essa2 M.D. 1Department of neurosurgery, Faculty of Medicine, Assiut University, Assiut, Egypt 2Department of neurosurgery, Faculty of Medicine, Assiut University, Assiut, Egypt Background: Acute subdural hematoma (ASDH) is considered the most common traumatic brain mass lesion. Its prognosis is still grave despite the improvements in treatment modalities. Its mortality rate was reported to be around 60% until the 1990s. In the last decade, ASDH mortality rate was reduced to the level of 20-40%. Standard treatment to decrease intracranial tension via hematoma evacuation associated with decompressive craniotomy and followed by ICU management. Objective: To evaluate the outcome and prognostic factors in patients of acute subdural hematoma treated by surgical evacuation and decompressive craniotomy. Also, outcome of cranioplasty by repositioning of patients own bone or by synthetic mesh methods is evaluated. Patients and methods: It is one year retrospective study. It was conducted on 53 patients, in trauma unit, Assiut university hospitals. We report time lag between trauma and performed surgery, initial Glasgow coma scale (GCS), age, sex and presence of other intracranial pathologies. Outcome assessment based on Glasgow outcome scale (GOS) and follow up extended for 6 months. We include those patients with only (isolated) head trauma, shift of midline more than 5 mm in CT brain. We excluded patients with GCS 3 and fixed dilated pupils as well as patients with GCS higher than 12. We did decompressive craniotomy and duroplasty in all patients. Bone flap of decompressive craniotomy is situated in the abdomen. All functionally recovered patients were submitted for cranioplasty with either replacing patient own bone or by Titanium mesh. Results: We had 39 males and 14 females. Age ranged between 7 and 65 years old. 23 deaths, 10 persistent vegetative state, 10 severe disability, 8 moderate disability and 2 good recovery. The outcome analysis was based on 6 month follow up Conclusion: Acute subdural hematoma is a very serious condition. Mortality and morbidity is intimateley related to GCS on admission. Presence of associated cerebral pathology increases mortality and morbidity of patients with posttraumatic acute subdural hematoma. Early evacuation of posttraumatic acute subdural hematoma with decompressive craniotomy is an important method to control raised intracranial tension, reduce shift of midline and very beneficial in decreasing mortality and morbidity. Regards infection and avoiding bone flap resorbtion, Titanium mesh is better than patient own bone during cranioplasty after patient recovery.

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