Resuscitation from experimental heatstroke by brain cooling therapy

We have used hypothermic retrograde jugular venous flush to cool the brain previously and to provide better resuscitation than peripheral cold saline infusion during heatstroke in the rat. The current study was performed to assess the effects of brain cooling further on production of reactive nitrogen species, reactive oxygen species, tumor necrosis factor-alpha, and interleukin-10 in both serum and brain during heatstroke. Rats, under general anaesthesia, were randomized into the following groups and given: (a) 36 degrees C or (b) 4 degrees C saline infusion in the external jugular vein immediately after onset of heatstroke. They were exposed to an ambient temperature of 43 degrees C for exactly 70 min to induce heatstroke. When the 36 degrees C saline-treated rats underwent heat stress, their survival time values were found to be 21-25 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline greatly improved survival (226-268 min). Compared with the normothermic controls, the 36 degrees C saline-treated heatstroke rats displayed higher levels of brain temperature, intracranial pressure, serum and hypothalamic nitric oxide metabolite, tumor necrosis factor-alpha and dihydroxybenzoic acid as well as hypothalamic inducible nitric oxide synthase immunoreactivity. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and hypothalamic levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-alpha, and dihydroxybenzoic acid in both the serum and the hypothalamus, and the increased levels of hypothalamic inducible nitric oxide synthase immunoreactivity occurred during heatstroke were significantly suppressed by brain cooling. Although the serum and hypothalamic interleukin-10 maintained at a negligible level before stress, they were significantly elevated by brain cooling during heatstroke. These findings suggest that brain cooling may resuscitate persons who had heatstroke by decreasing overproduction of reactive nitrogen species, tumor necrosis factor-alpha, reactive oxygen species and cerebrovascular dysfunction, but increasing production of interleukin-10.     

Resuscitation from experimental heatstroke by estrogen therapy

OBJECTIVE: We investigated the effect of estrogen therapy on inflammatory responses, cardiovascular functions, and survival in a rat model of heatstroke. DESIGN: Controlled, prospective study. SETTING: Hospital medical research laboratory. SUBJECTS: Sprague-Dawley rats (280-312 g of body weight, males and females). INTERVENTIONS: Four major groups of anesthetized rats were designated for experiments: a) vehicle-treated male rats; b) vehicle- or premarin-treated estrus female rats; c) vehicle- or premarin-treated ovariectomized rats; and d) vehicle- or premarin-treated leuprolide-treated rats. All animals were exposed to heat stress (ambient temperature 43 degrees C for 70 mins) and then allowed to recover at room temperature (24 degrees C). Their survival time (interval between the onset of heatstroke and animal death) and physiologic and biochemical variables were monitored. Vehicle (normal saline 1 mL/kg of body weight, intravenously) or premarin (1 mg/mL/kg of body weight, intravenously) was administered 70 mins after initiation of heat stress. Ovariectomy or leuprolide (100 mug/kg/day, subcutaneously) injection was conducted 4 wks before the start of heat stress experiments. Another group of rats were exposed to 24 degrees C and used as normothermic controls. MEASUREMENTS AND MAIN RESULTS: Compared with the estrus female rats, the ovariectomized rats, the leuprolide-treated rats, and male rats all had lower levels of plasma estradiol and lower survival time values. However, after an intravenous dose of premarin, both the plasma estradiol and survival time values were significantly increased. Compared with the normothermic controls, the vehicle-treated male and ovariectomized rats all displayed higher levels of serum tumor necrosis factor-alpha, which could be suppressed by premarin therapy. In contrast, the serum levels of IL-10 in these groups were significantly elevated by premarin during heatstroke. Furthermore, the heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, and cerebral hypoperfusion, hypoxia, and ischemia were significantly attenuated by premarin therapy in ovariectomized rats. CONCLUSIONS: We successfully demonstrated that estrogen replacement may improve survival during heatstroke by ameliorating inflammatory responses and cardiovascular dysfunction.     

Resuscitation from experimental heatstroke by hyperbaric oxygen therapy

OBJECTIVE: Heatstroke is characterized by hyperthermia, vasoplegic shock, and cerebral ischemia and hypoxia. Hyperbaric oxygen (HBO) has been shown to reduce brain ischemia and behavioral dysfunction during cerebral artery occlusion. The efficacy of HBO therapy for resuscitation from heatstroke remains to be determined in the laboratory. DESIGN: Anesthetized rats were randomized to several groups and administered: 1) no resuscitation (normobaric air) after onset of heatstroke, 2) HBO for 1 hr (100% oxygen at 253 kPa for 1 hr), 3) cyclic HBO intermitted by a 5-min air break for 1 hr of treatment (100% oxygen at 253 kPa), 4) hyperbaric air (air at 253 kPa for 1 hr), 5) normobaric hyperoxia (100% oxygen at 101 kPa for 1 hr), or 6) 8% HBO (hyperbaric 8% oxygen at 253 kPa for 1 hr). SETTING: Laboratory investigation. SUBJECTS: Sprague-Dawley rats (300- to 400-g males). INTERVENTIONS: Rats were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their colonic temperature; mean arterial pressure; heart rate; arterial blood levels of pH, Paco2, Pao2, So2%, and tumor necrosis factor-alpha; the cortical levels of ischemic and damage markers, and cortical neuronal damage scores were determined. The moment at which mean arterial pressure began to decrease from peak levels was arbitrarily taken as the onset of heatstroke. MAIN RESULTS: Survival time (interval between onset of heatstroke and animal death) was 19 +/- 1 (n = 10), 131 +/- 18 (n = 14), 159 +/- 28 (n = 13), 72 +/- 14 (n = 10), 68 +/- 12 (n = 10), and 45 +/- 11 (n = 10) mins, respectively, for normobaric air, HBO for 1 hr, cyclic HBO, hyperbaric air, normobaric hyperoxia, and 8% HBO groups. The heatstroke induced arterial hypotension and bradycardia, decreased arterial levels of pH, Pao2, and So2%, increased arterial levels of tumor necrosis factor-alpha, and increased values of cellular ischemia and damage markers. In addition, neuronal damage scores in the cortex were significantly reduced by HBO for 1 hr and cyclic HBO resuscitation. CONCLUSION: We successfully demonstrated that HBO and, to some extent, hyperbaric air, normobaric hyperoxia, or HBO 8% was found beneficial in resuscitating rats with experimental heatstroke. HBO effectively reduced heatstroke-induced arterial hypotension, hypoxia, plasma tumor necrosis factor-alpha overproduction, and cerebral ischemia and damage and improved survival.     

颅脑损伤的作业治疗

本文概括介绍了颅脑外伤的发病率、病因、分型、严重程度评价和临床表现 , 作业治疗的定义 , 作用和理论基础 , 颅脑损伤的作业治疗原则 , 治疗程序 , 不同时期 ( 急性期 , 恢复期和后期 ) 的治疗目的和治疗方法 .     

Resuscitation from hemorrhagic shock with HBOC-201 in the setting of traumatic brain injury

Outcomes after mild or moderate head trauma are worsened with associated hypotension, and secondary brain injury can be reduced with timely resuscitation. This study was performed to investigate HBOC-201 as a resuscitation therapy in a combined hemorrhagic shock and brain injury model. Anesthetized rats sustained moderate brain injury using a controlled cortical impact device, followed by rapid hemorrhage to a mean arterial pressure of 30 mmHg. After 30 min of hypotension, animals were resuscitated with HBOC-201, autologous shed blood (SB), or lactated Ringer solution (LR). Brain injury was assessed by measurements of cerebral blood flow (CBF) and cerebral vasoreactivity to hypercapnia (CVH) using a laser Doppler flowmeter. Contusion volume was evaluated histologically, and cerebral edema was determined by total water content. The HBOC rats required significantly less resuscitation volume versus LR and SB. The CBF was significantly diminished at 60 min after resuscitation with HBOC (70.1% +/- 3.8% baseline) compared with LR (105.8% +/- 10.1% baseline; P < 0.01) and SB (96.8% +/- 5% baseline; P < 0.05). The CVH was preserved in the HBOC and SB groups. The CVH was significantly diminished compared with baseline in the LR group at 30 min after resuscitation and showed a significant loss compared with HBOC at 60 min after resuscitation. The contusion volume for HBOC (45.1 mm3) and SB (35.1 mm3) was less than LR (63.5 mm3, P < 0.01). Although CBF was diminished after resuscitation in the HBOC group, HBOC-treated animals maintained CVH and experienced significantly smaller contusion volume than those treated with LR. These results suggest that resuscitation with HBOC-201 protects autoregulatory mechanisms and may reduce secondary brain injury in traumatic brain injury.     

脑外伤患者的运动疗法

脑外伤后由于脑的损伤部位不同 , 其运动障碍表现多种多样 , 使脑外伤后康复难度加大 ; 脑外伤后的运动治疗需根据不同运动障碍类型采取不同治疗方法 . 本文详细介绍了脑外伤后不同运动障碍类型的运动疗法 .     

Severe traumatic brain injury from unmotorized scooter

The popularity and use of unmotorized, foot-propelled scooters has risen dramatically in the last few years. Increasing reports of traumatic injuries from these scooters have paralleled their commercial sales and success in this country and worldwide. We report a case of a previously healthy 48-year-old woman who suffered a severe traumatic brain injury while riding one of these scooters, resulting in a devastating neurologic outcome and permanent vegetative state. This case emphasizes the importance of public awareness regarding the potential dangers and the need for appropriate precautions and protective gear when riding these recreational devices.     

Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design

Ouellet M-C, Morin CM. Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design.

Objective

To test the efficacy of a cognitive-behavioral therapy (CBT) for insomnia in persons having sustained traumatic brain injury (TBI).

Design

Single-case design with multiple baselines across participants.

Setting

Outpatient rehabilitation center.

Participants

Eleven subjects having sustained mild to severe TBI who developed insomnia after the injury.

Intervention

Eight-week CBT for insomnia including stimulus control, sleep restriction, cognitive restructuring, sleep hygiene education, and fatigue management.

Main Outcome Measures

Total wake time, sleep efficiency, and diagnostic criteria.

Results

Visual analyses, corroborated by intervention time series analyses and t tests, revealed clinically and statistically significant reductions in total wake time and sleep efficiency for 8 (73%) of 11 participants. An average reduction of 53.9% in total wake time was observed across participants from pre- to post-treatment. Progress was in general well maintained at the 1-month and 3-month follow-ups. The average sleep efficiency augmented significantly from pretreatment (77.2%) to post-treatment (87.9%), and also by the 3-month follow-up (90.9%). Improvements in sleep were accompanied by a reduction in symptoms of general and physical fatigue.

Conclusions

The results of this study show that psychologic interventions for insomnia are a promising therapeutic avenue for TBI survivors.     

磁共振弥散张量成像技术对创伤性脑损伤的评价

目的：本研究通过分析不同损伤程度的创伤性脑损伤（TBI）患者弥散张量成像（DTI）动态变化的规律,评价其与临床资料的相关性,探讨其在反映TBI的损伤程度及预后方面的价值。方法：对59例共计89人次的TBI患者和60例对照者行常规MRI、DTI检查。测量对照者及TBI患者（急性期、亚急性期、伤后1~3月）胼胝体、内囊、脑干的FA值、ADC值。比较对照组和TBI患者间以及轻、中重度患者间的差异,将不同时期各观察区的测量值与GCS评分行相关性分析,并在不同预后组之间进行比较。结果：TBI患者多数观察区的FA值呈伤后持续减低趋势,FA值与GCS评分呈明显正相关,预后较差者FA值的减低更为明显。伤后1~3月时胼胝体、内囊处的FA值仍具有上述统计学意义。ADC值在伤后呈双相性改变,与GCS、GOS评分间相关性不及FA值。结论：FA值的减低与TBI患者的损伤程度之间具有良好的相关性,并能提示预后改变。在伤后1~3月时,DTI仍能反映出白质纤维束的损伤。ADC值与损伤程度、预后之间的相关性不及FA值敏感、准确。     

Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute

The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of <110 beats/min. In Series 2, TBI (4-5 ATM) was followed by a 35% hemorrhage. At 60 min post-TBI, initial resuscitation consisted of either 500 mL of DCLHb (n = 6) or 500 mL of saline (n = 5). This was followed by saline supplements to all pigs to maintain a SAP of >100 mmHg and a HR of <110 beats/min. In Series 1, most systemic markers of resuscitation (e.g., SAP, HR, cardiac output, filling pressures, lactate, etc.) were normalized, but there were 0/7 vs. 5/13 deaths within 5 h (P = 0.058) with blood vs. saline. At constant arterial O2 saturation (SaO2), mixed venous O2 saturation (SvO2), cerebral perfusion pressure (CPP), and cerebral venous O2 saturation (ScvO2) were all higher, intracranial pressure (ICP) was lower, and CO2 reactivity was preserved with blood vs. saline (all P < 0.05). In Series 2, SAP, ICP, CPP, and lactate were higher with DCLHb vs. saline (all P< 0.05). Cardiac output was lower even though filling pressure was markedly elevated with DCLHb vs. saline (both P< 0.05). Neither SvO2 nor cerebrovascular CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P < 0.05). All survived at least 72 h with neuropathologic changes that included sub-arachnoid hemorrhage, midline cerebellar necrosis, and diffuse axonal injury. These changes were similar with DCLHb vs. saline. Thus, whole blood was more effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.     

Treating childhood traumatic brain injury with autologous stem cell therapy

Introduction: Neonatal traumatic brain injury (TBI) is a significant cause of developmental disorders. Autologous stem cell therapy may enhance neonatal brain plasticity towards repair of the injured neonatal brain.

Areas covered: The endogenous neonatal anti-inflammatory response can be enhanced through the delivery of anti-inflammatory agents. Stem cell therapy stands as a robust approach for sequestering the inflammation-induced cell death in the injured brain. Here, we discuss the use of umbilical cord blood cells and bone marrow stromal cells for acute and chronic treatment of experimental neonatal TBI. Autologous stem cell transplantation may dampen neuroinflammation. Clinical translation of this stem cell therapy will require identifying the therapeutic window post-injury and harvesting ample supply of transplantable autologous stem cells. Stem cell banking of cryopreserved cells may allow readily available transplantable cells and circumvent the unpredictable nature of neonatal TBI. Harnessing the anti-inflammatory properties of stem cells is key in combating the progressive neurodegeneration after the initial injury.

Expert opinion: Combination treatments, such as with hypothermia, may enhance the therapeutic effects of stem cells. Stem cell therapy has immense potential as a stand-alone or adjunctive therapy for treating neuroinflammation associated with neonatal TBI acutely and for preventing further progression of the injury.     

Mild traumatic brain injury

Mild head injury is a common emergency presentation. Previously medical attention has focused on risk of injury requiring surgical intervention. The importance of long term sequelae in patients not requiring surgical intervention has now been recognised. It is not clear, however, how frequently this occurs, which patients are at risk and whether interventions improve outcome. The symptoms associated with mild traumatic brain injury have an organic basis. Some people will be helped by strategies to deal with these symptoms. Emergency physicians should develop better methods to ensure adequate screening in the emergency department to target at risk groups and introduce interventions which are proven to be effective.     

Severe traumatic brain injury

In western countries, injuries remain the leading cause of death in young adults (Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry 1996; 60: 362-369). Worldwide, injuries are estimated to account for 15% of the burden of death and disability, and are projected to account for 20% in 2020 (Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and Development (Document TDR/Gen/96.1). Geneva: World Health Organisation, 1996). In developing countries road traffic injuries in particular are increasing in incidence and injuries are projected to be the third leading cause of death and disability worldwide by 2020 (Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and Development (Document TDR/Gen/96.1). Geneva: World Health Organisation, 1996). Head injury accounts for up to half of all deaths from trauma (Kraus J. Epidemiology of head injury. In: Cooper PR, Ed. Head Injury, 3rd ed. Baltimore, MD: William Wilkins, 1993), and in addition to causing death often causes severe and long-lasting functional impairment in survivors.     

硫酸镁治疗重型颅脑外伤的疗效

目的:研究颅脑外伤(TBI)后早期补充硫酸镁对TBI的疗效。方法:将我科3年来收治的94例重型TBI患者分为硫酸镁治疗组、硫酸镁+利多卡因治疗组及对照组。硫酸镁治疗组除常规治疗外还给予硫酸镁2g(16mmol)稀释至100mL于15min内推注+硫酸镁7.8g(65mmol)稀释至500mL静滴24h。硫酸镁+利多卡因治疗组除了以上述方法应用硫酸镁外,加用利多卡因1mg/(kg·h)维持24h。对照组除不补充硫酸镁和利多卡因之外其余治疗同以上两组。检测所有患者入院及3d时血镁水平、入院和入院1周时的血神经元烯醇化酶(NSE)含量,6个月后以格拉斯哥预后评分(GOS)来评估各组治疗结果。结果:各组重型TBI患者在受伤后1周时的血NSE水平无明显差异,各组重型TBI患者伤后6个月时GOS的结果无明显差异。结论:本研究未发现TBI后早期补充硫酸镁能明显改善重型TBI的治疗效果。     

Gastroparesis following traumatic brain injury and response to metoclopramide therapy

Most studies on nutrition in patients with traumatic brain injury (TBI) have focused on the hypermetabolic state immediately after trauma, or the swallowing disorders that frequently follow acute TBI. A less well-known sequela, however, is gastroparesis, which generally manifests itself when patients have advanced from nasogastric to oral feeding programs. Case histories of four patients are reported, all of whom responded to therapeutic intervention with metoclopramide. Results of a radionuclide gastric emptying study, before and after metoclopramide therapy, are presented. The etiologic and physiologic mechanisms behind this disorder are unclear, but demonstration of this disorder and other clinical trials with metoclopramide appear to deserve further consideration in the nutritionally compromised TBI patient.     

犬脑外伤超声造影的初步研究

目的探讨灰阶超声造影在实验犬脑外伤诊断中的应用价值。方法 6只实验犬制造脑外伤模型。分别于伤后即刻、伤后15min、伤后30min、伤后1h行二维超声及超声造影检查,观察损伤灶回声、损伤范围,与病理学检查相比较。结果所有动物经病理证实均形成同侧损伤灶,其中脑内血肿2只,脑挫裂伤4只。二维超声脑损伤灶均表现为不规则团状高回声,边界不清;超声造影显示,脑内血肿表现为始终无增强区,边界清楚;脑挫裂伤灶表现为早期无-低增强区,随后周边及内部可见造影剂缓慢少量充盈,增强强度始终低于对侧正常脑实质;脑外伤灶大小超声造影测值与病理标本测值对照,差异无统计学意义(P0.05);伤后30min及伤后1h损伤灶持续增大,与伤后即刻相比差异有统计学意义(P0.05)。结论超声造影有助于显示脑损伤范围、类型,超声造影结合常规超声可以实现脑外伤的动态观察。     

经颅多普勒监测下过度通气治疗重型颅脑损伤患者的临床研究

目的探讨经颅多普勒（TCD）监测下调整过度通气治疗策略对重症颅脑损伤（sTBI）患者的疗效。 方法将59例sTBI患者分为对照组（30例）和实验组（29例）,对照组采用过度通气治疗,实验组在对照组基础上,根据TCD监测的脑血管痉挛（CVS）程度调整通气治疗策略。监测两组患者治疗前后大脑中动脉（MCA）的平均血流速度（Vm）,并计算治疗前后的平均血流速度变化值（ΔVm）。同时,将两组sTBI患者分为无CVS组（Vm<120 cm/s）、轻度CVS组（120 ≤ Vm<140 cm/s）、中重度CVS组（Vm ≥ 140 cm/s）,对各亚组间的ΔVm进行比较。采用格拉斯哥结局量表（GOS）对两组患者治疗6个月后的疗效进行评估。 结果实验组患者ΔVm显著高于对照组患者[22.0（13.0,39.5）cm/s vs. 10.0（7.0,26.3）cm/s,H = 2.527,P = 0.012]。对照组和实验组不同CVS程度患者间ΔVm比较,差异有统计学意义（H = 20.276,P = 0.001）;实验组中,轻度CVS组及中重度CVS组均显著高于无CVS组[23.0（21.5,41.0）、40.0（22.5,52.0）、13.0（9.8,18.0）cm/s],且中重度CVS组更高（P均<0.05）;且对于中重度CVS患者,实验组的ΔVm明显较对照组增加[40.0（22.5,52.0）cm/s vs. 9.0（8.0,31.0）cm/s,P<0.05]。治疗6个月后实验组GOS评分整体优于对照组（u = 2.059,P = 0.045）。 结论根据TCD监测结果调整过度通气治疗策略有利于缓解CVS,改善sTBI患者的疗效。