Recovery of neurosurgical high-frequency electroporation injury in the canine brain can be accelerated by 7,8-dihydroxyflavone.

BACKGROUND: Although traumatic brain injury (TBI) occurs in a very short time, the biological consequence of a TBI, such as Alzheimer's disease, may last a lifetime. To date, effective interventions are not available to improve recovery from a TBI. Herein we aimed to ascertain whether recovery of neurosurgical high-frequency irreversible electroporation (HFIRE) injury in brain tissues can be accelerated by 7,8-dihydroxyflavone (7,8-DHF). METHODS: The HFIRE injury was induced in the right parietal cortex of 8 adult healthy and neurologically intact male dogs. Two weeks before HFIRE injury, each dog was administered orally with or without 7,8-DHF (30 mg/kg) once daily for consecutive 2 weeks (n = 4 for each group). The values of blood-brain barrier (BBB) disruption, brain edema, and cerebral infarction volumes were measured. The concentrations of beta-amyloid, interleukin-1ß, interleukin-6 and tumor necrosis factor-α in the cerebrospinal fluid were measured biochemically. RESULTS: The BBB disruption, brain edema, infarction volumes, and maximal cross-section area caused by HFIRE injury in canine brain were significantly attenuated by 7,8-DHF therapy (P < 0.0001). Additionally, 7,8-DHF significantly reduced the HFIRE-induced cerebral overproduction of beta-amyloid and proinflammatory cytokines in the cerebrospinal fluid (P < 0.0001) in dogs with HFIRE. CONCLUSIONS: Recovery of neurosurgical HFIRE injury in canine brain tissues can be accelerated by 7,8-DHT via ameliorating BBB disruption as well as cerebral overproduction of both beta-amyloid and proinflammatory cytokines.

7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection.

BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.

Effects of post-discharge nurse-led telephone supportive care for patients with chronic kidney disease undergoing peritoneal dialysis in China: a randomized controlled trial.

BACKGROUND: Patients with end-stage renal failure (ESRF) need integrated health care to maintain a desirable quality of life. Studies suggest that post-discharge nurseled telephone support has a positive effect for patients suffering from chronic diseases. But the post-discharge care is under-developed in mainland China and the effects of post-discharge care on patients with peritoneal dialysis have not been conclusive. AIM: The purpose of this study is to test the effectiveness of postdischarge nurse-led telephone support on patients with peritoneal dialysis in mainland China. METHODS: A randomized controlled trial was conducted in the medical department of a regional hospital in Guangzhou. 135 patients were recruited, 69 in the study group and 66 in the control group. The control group received routine hospital discharge care. The study group received post-discharge nurse-led telephone support. The quality of life (Kidney Disease Quality of Life Short Form, KDQOL-SF), blood chemistry, complication control, readmission and clinic visit rates were observed at three time intervals: baseline before discharge (T1), 6 (T2) and 12 (T3) weeks after discharge. RESULTS: Statistically significant effects were found for symptom/problem, work status, staff encouragement, patient satisfaction and energy/fatigue in KDQOL-SF and 84-day (12-week) clinic visit rates between the two groups. The study group had more significant improvement than the control group for sleep, staff encouragement at both T2 and T3, and pain at T2 and patient satisfaction at T3. No significant differences were observed between the two groups for the baseline measures, other dimensions in KDQOL-SF, blood chemistry, complication control, readmission rates at all time intervals and clinic visit rates at the first two time intervals. CONCLUSIONS: Post-discharge nurse-led telephone support for patients undergoing peritoneal dialysis is effective to enhance patients' well-being in the transition from hospital to home in mainland China.

Therapeutic effects of melatonin on heatstroke-induced multiple organ dysfunction syndrome in rats.

Melatonin reportedly exerts beneficial effects to attenuate multiple organ dysfunction syndrome (MODS) in septic shock. Heatstroke resembles septic shock in many aspects. Thus, this study was performed on the anesthetized rats by using heat exposure to induce heatstroke-associated MODS. We evaluated the effect of melatonin, a versatile molecule synthesized in the pineal gland and in many organs, in heatstroke rats and showed that melatonin (0.2-5.0 mg/kg of body weight, i.v., immediately after the start of heat stress) significantly (i) attenuated hyperthermia, hypotension and hypothalamic ischemia and hypoxia, (ii) reduced plasma index of the toxic oxidizing radicals like nitric oxide metabolites and hydroxyl radicals, (iii) diminished plasma index of hepatic and renal dysfunction like creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, (iv) attenuated plasma systemic inflammation response molecules like soluble intercellular and lesion molecule-1, E-selectin, tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6, (v) promoted plasma levels of an anti-inflammatory cytokine IL-10, (vi) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloperoxidase activity, and (vii) promoted the survival time to fourfold compared with the heatstroke alone group. Thus, melatonin could be a novel agent for the treatment of heatstroke animals or patients in the early stage.

[Immunohistochemical study of tumor necrosis factor-alpha expression in the lungs and small intestines in hyperthermia-LPS co-stressed rats].

OBJECTIVE: To investigate the effects of co-exposure to hyperthermia and lipopolysaccharides (LPS) on tumor necrosis factor-alpha (TNF-alpha) expression in the lungs and small intestines of rats. METHODS: Male pathogen-free Wistar rats were randomly assigned into saline-injected normothermic control (C), saline heat exposure (H), LPS normothermic control (L), and LPS plus heat exposure (HL) groups. The rats in H and HL groups were exposed in a chamber at an ambient dry bulb temperature (Tdb) of 35.0-/+0.5 degrees celsius;, and those in C and L groups to 26-/+0.5 degrees celsius;. In L and HL groups, the rats were given an intravenous injection of LPS 10 mg/kg via the tail vein to induce endotoxemia, and those in C and H group received 10 ml/kg injection. The plasma levels of sTNFrI and sTNFrII were detected at different time points using ELISA. The expression of TNF-alpha in the lungs and small intestines was detected by immunohistochemical SABC method, and the damage of the lungs and small intestines evaluated histologically 120 min after the treatment. RESULTS: Co-exposure to hyperthermia and LPS caused significantly enhanced expressions of TNF-alpha and its receptor sTNFrI and sTNFrII in the plasma and tissues and obvious histopathological damage in the lung and small intestines. CONCLUSION: Co-stress of hyperthermia and LPS-induced toxicity is associated with the expression of TNF-alpha in the lung and small intestines.

[Immunohistochemical study of TNF-alpha expression in the kidney of rats with lipopolysaccharide and heat stresses].

OBJECTIVE: To investigate the effects of co-exposure of LPS and heat on TNF-alpha expression in rat kidneys. METHODS: Male pathogen-free Wistar rats were randomly assigned in saline-injected normothermic control (C group), saline-injected heat exposure (H group), LPS-injected normothermic control (L group), and LPS-injected heat exposure (HL group). The rats in H and HL groups were exposed in a chamber at an ambient dry bulb temperature (Tdb) of 35.0-/+0.5 degrees, and those in C and L groups were exposed to a Tdb of 26-/+0.5 degrees. The rats in L and HL groups were given an intravenous injection of LPS (10 mg/kg) via the tail vein to induce endotoxemia, and equivalent normal saline was injected in C and H groups. TNF-alpha expression in the kidney was detected by immunohistochemical SABC method, and the renal damage was evaluated histologically at 120 min after the treatment. RESULTS: Co-exposure of the rats with LPS and heat caused significantly enhanced TNF-alpha expression and histopathological damage in the kidneys. CONCLUSION: LPS combined with heat exposure causes renal toxicity, while is closely associated with the expression of TNF-alpha in the kidneys.

Activated protein C can be used as a prophylactic as well as a therapeutic agent for heat stroke in rodents.

The present study was attempted to assess the prophylactic and the therapeutic effect of human recombinant activated protein C (APC; drotrecogin-alpha, activated) in experimental heat stroke. Anesthetized rats were divided into two groups and given vehicle solution 1 h before the start or immediately after the termination of heat stress (isotonic sodium chloride solution, 2 mL kg(-1) of body weight, i.v.) or APC (1-10 mg in 2 mL of isotonic sodium chloride solution per kilogram of body weight, i.v.). They were exposed to ambient temperature of 40 degrees C for 100 min to induce heat stroke. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 57 to 71 min. Pretreatment or treatment with APC significantly increased survival time (122-221 min). All vehicle-pretreated heat stroke animals displayed systemic inflammation (evidenced by increased TNF-alpha, IL-1alpha, and IL-6) and activated coagulation (evidenced by increased levels of activated partial thromboplastin time, prothrombin time, and D-dimer and decreased levels of both platelet count and protein C). Biochemical assay also revealed that both renal and hepatic dysfunction (e.g., increased plasma levels of blood urea nitrogen, creatinine, adenine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) were noted during heat stroke. A significant decrease in both cerebral blood flow and partial pressure of oxygen in hypothalamus were also observed in vehicle-pretreated heat stroke animals. These heat stroke reactions were all significantly reduced by pretreatment or treatment with human recombinant APC. The results indicate that human recombinant APC can be used as a prophylactic and a therapeutic agent for experimental heat stroke by ameliorating systemic inflammation, hypercoagulable state, and multiple organ dysfunction.