mobic and Brain-Injuries

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aβ, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aβ, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.

Topics: Animals; Brain; Brain Injuries; Cyclooxygenase 2; Female; Humans; Inflammation; Lipopolysaccharides; Meloxicam; Memory Disorders; Necrosis; Pregnancy; Preimplantation Diagnosis; Prenatal Exposure Delayed Effects; Rats; Transcription Factors

OBJECTIVE To observe the protective effect of meloxicam against acute radiation-induced brain injury in rats.. Fifty-four SD rats were randomly divided into blank control group, radiation group (20 Gy) and therapy group (20 Gy radiation followed by 10 mg/kg meloxicam treatment). The whole brain of SD rats in the radiation and therapy groups were vertically irradiated by 6 MeV electron beam at a dose of 20 Gy. One, 3 and 7 days after irradiation, the morphological changes of hippocampal neurons were observed using HE staining, and the expressions of cyclooxygenase-2 (COX-2) mRNA and protein were detected by RT-PCR and immunohistochemistry, respectively.. Compared with the blank control group, the radiation group showed that the neuron swelling and vascular endothelial cell edema as well as space enlargement around the capillaries. Both neuron swelling and vascular endothelial cell injury in the therapy group were slighter than those in the radiation group. Compared with the blank control group, the levels of COX-2 mRNA and protein in the radiation and therapy groups increased obviously one day after irradiation (P<0.05), and compared with the radiation group, the levels decreased obviously in the therapy group (P<0.05); 3 and 7 days after irradiation, the levels of COX-2 mRNA and protein among the 3 groups had no statistical differences (P>0.05).. The early use of meloxicam can reduce the brain injury induced by radiation. Its protective effect may be related to the relief of vascular endothelial cell injury and the decreased expression of COX-2.

Topics: Animals; Brain; Brain Injuries; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Gene Expression Regulation, Enzymologic; Male; Meloxicam; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thiazines; Thiazoles

Meloxicam is a cyclo-oxygenase-2 (COX-2) preferential non-steroidal anti-inflammatory drug with very effective analgesic and anti-inflammatory effects in swine. Previous reports in piglets have demonstrated that meloxicam also inhibits COX-1 and reduces production of thromboxane significantly. We use preinjury analgesia in our immature swine (3-5-day-old piglets) model of brain injury using rapid head rotations without impact. In 23 consecutive subjects we found that premedication with meloxicam (n = 6) produced a significantly higher mortality rate (5/6 or 83%) than buprenorphine (n = 17, 1/17 or 6%, P < 0.02). On gross neuropathological examination of the meloxicam-treated swine, we observed massive subdural and subarachnoid bleeding which were not present in buprenorphine-premedicated animals. To our knowledge there are no previous reports in swine of increased bleeding or platelet inhibition associated with meloxicam administration and further research is needed to define mechanisms of action in piglets. We caution the use of meloxicam in swine when inhibition of platelet aggregation might adversely affect refinement of experimental research protocols, such as in stroke, trauma and cardiac arrest models.

Topics: Amyloid beta-Protein Precursor; Animals; Animals, Newborn; Brain; Brain Injuries; Buprenorphine; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Hematoma, Subdural; Injections, Intramuscular; Meloxicam; Premedication; Subarachnoid Hemorrhage; Survival Rate; Swine; Thiazines; Thiazoles

The overproduction of reactive oxygen species and resultant damage to cellular proteins or lipids of cell membranes and DNA by free radicals are the underlying mechanisms of many neuropathologies. Cyclooxygenase-2 (COX-2) inhibitors have been suggested to be neuroprotective by reducing prostanoid and free radical synthesis, or by directing arachidonic acid metabolism through alternate pathways. This study investigated the putative neuroprotective effect of the COX-2 inhibitor, meloxicam, in a rat model of diffuse brain injury.. Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g(-1) m weight-height impact. The groups were: control, meloxicam (2 mg/kg, i.p.), trauma and trauma + meloxicam (2 mg/kg, i.p.). Forty-eight hours after the injury, neurological examination scores were measured, the animals were decapitated and brain tissues were taken. Brain edema and blood-brain barrier (BBB) permeability were evaluated by wet-dry weight method and Evans blue (EB) extravasation respectively. In brain tissues, malonedialdehyde, glutathione, myeloperoxidase and Na/K-ATPase levels were measured.. The neurological examination scores mildly increased in trauma groups 48 hours after the induction of trauma. Meloxicam treatment improved the altered neurological status. The trauma caused a significant increase in brain water content that was partially reversed by meloxicam. Meloxicam also reduced the EB extravasation indicating the preservation of the BBB integrity. Meloxicam treatment also significantly reduced the increase in malondialdehyde and myeloperoxidase levels and restored glutathione content of the brains that had been significantly increased after trauma.. Meloxicam exerts neuroprotective effect by preserving BBB permeability and by reducing brain edema (probably by its anti-inflammatory properties) in the diffuse brain injury model.

Topics: Analysis of Variance; Animals; Blood-Brain Barrier; Brain Chemistry; Brain Injuries; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Glutathione; Male; Malondialdehyde; Meloxicam; Neurochemistry; Neurologic Examination; Permeability; Peroxidase; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Thiazines; Thiazoles