Acute Nervous System Injury Research Articles

Fever in the Neurointensive Care Unit

AbstractFever occurs commonly in patients admitted to the neurocritical care unit. An increase in the body temperature is known to have deleterious effects on patients with acute nervous system injury and in most cases is associated with an increase in mortality and morbidity of these patients. There are multiple causes of fever in these patients. Due to the potentially devastating effects of fever in patients with cerebral diseases, it warrants treatment in every case. In all patients with acute cerebral damage, treatment of fever and maintenance of euthermia is important to obtain a better functional recovery and to limit any further secondary insult to the brain. This review highlights the etiology and pathophysiology of fever in neurocritical care unit patients, the effects on various organ systems and associated systemic complications, and the evaluation and different therapeutic options available for the management of fever in this patient subset.

A fragment of adhesion molecule L1 is imported into mitochondria, and regulates mitochondrial metabolism and trafficking.

The cell adhesion molecule L1 (also known as L1CAM) plays important roles in the mammalian nervous system under physiological and pathological conditions. We have previously reported that proteolytic cleavage of L1 by myelin basic protein leads to the generation of a 70 kDa transmembrane L1 fragment (L1-70) that promotes neuronal migration and neuritogenesis. Here, we provide evidence that L1-70 is imported from the cytoplasm into mitochondria. Genetic ablation of L1, inhibition of mitochondrial import of L1-70 or prevention of myelin basic protein-mediated generation of L1-70 all lead to reduced mitochondrial complex I activity, and impaired mitochondrial membrane potential, fusion, fission and motility, as well as increased retrograde transport. We identified NADH dehydrogenase ubiquinone flavoprotein 2 as a binding partner for L1, suggesting that L1-70 interacts with this complex I subunit to regulate complex I activity. The results of our study provide insights into novel functions of L1 in mitochondrial metabolism and cellular dynamics. These functions are likely to ameliorate the consequences of acute nervous system injuries and chronic neurodegenerative diseases.

Diffusion MRI in acute nervous system injury

Diffusion weighted magnetic resonance imaging (DWI) and related techniques such as diffusion tensor imaging (DTI) are uniquely sensitive to the microstructure of the brain and spinal cord. In the acute aftermath of nervous system injury, for example, DWI reveals changes caused by injury that remains invisible on other MRI contrasts such as T2-weighted imaging. This ability has led to a demonstrated clinical utility in cerebral ischemia. However, despite strong promise in preclinical models and research settings, DWI has not been as readily adopted for other acute injuries such as traumatic spinal cord, brain, or peripheral nerve injury. Furthermore, the precise biophysical mechanisms that underlie DWI and DTI changes are not fully understood. In this report, we review the DWI and DTI changes that occur in acute neurological injury of cerebral ischemia, spinal cord injury, traumatic brain injury, and peripheral nerve injury. Their associations with the underlying biology are examined with an emphasis on the role of acute axon and dendrite beading. Lastly, emerging DWI techniques to overcome the limitations of DTI are discussed as these may offer the needed improvements to translate to clinical settings.

Blockade of Astrocytic Calcineurin/NFAT Signaling Helps to Normalize Hippocampal Synaptic Function and Plasticity in a Rat Model of Traumatic Brain Injury.

Similar to microglia, astrocytes become strongly "activated" with neural damage and exhibit numerous morphologic/biochemical changes, including an increase in the expression/activity of the protein phosphatase calcineurin. Using adeno-associated virus (AAV) to inhibit the calcineurin-dependent activation of the transcription factor NFAT (Nuclear Factor of Activated T cells) selectively, we have shown that activated astrocytes contribute to neural dysfunction in animal models characterized by progressive/chronic neuropathology. Here, we show that the suppression of astrocytic calcineurin/NFATs helps to protect synaptic function and plasticity in an animal model in which pathology arises from a single traumatic brain injury. The findings suggest that at least some astrocyte functions impair recovery after trauma and may provide druggable targets for treating victims of acute nervous system injury.

Detection of acute nervous system injury with advanced diffusion-weighted MRI: a simulation and sensitivity analysis.

Diffusion-weighted imaging (DWI) is a powerful tool to investigate the microscopic structure of the central nervous system (CNS). Diffusion tensor imaging (DTI), a common model of the DWI signal, has a demonstrated sensitivity to detect microscopic changes as a result of injury or disease. However, DTI and other similar models have inherent limitations that reduce their specificity for certain pathological features, particularly in tissues with complex fiber arrangements. Methods such as double pulsed field gradient (dPFG) and q-vector magic angle spinning (qMAS) have been proposed to specifically probe the underlying microscopic anisotropy without interference from the macroscopic tissue organization. This is particularly important for the study of acute injury, where abrupt changes in the microscopic morphology of axons and dendrites manifest as focal enlargements known as beading. The purpose of this work was to assess the relative sensitivity of DWI measures to beading in the context of macroscopic fiber organization and edema. Computational simulations of DWI experiments in normal and beaded axons demonstrated that, although DWI models can be highly specific for the simulated pathologies of beading and volume fraction changes in coherent fiber pathways, their sensitivity to a single idealized pathology is considerably reduced in crossing and dispersed fibers. However, dPFG and qMAS have a high sensitivity for beading, even in complex fiber tracts. Moreover, in tissues with coherent arrangements, such as the spinal cord or nerve fibers in which tract orientation is known a priori, a specific dPFG sequence variant decreases the effects of edema and improves specificity for beading. Collectively, the simulation results demonstrate that advanced DWI methods, particularly those which sample diffusion along multiple directions within a single acquisition, have improved sensitivity to acute axonal injury over conventional DTI metrics and hold promise for more informative clinical diagnostic use in CNS injury evaluation.

SIRT1 Regulation Modulates Stroke Outcome

Silent information regulator 1 (SIRT1) is a NAD+-dependent histone deacetylase that represses gene expression and plays a role in longevity. SIRT1 responds to diverse stress conditions and regulates metabolism in nutrient deficiency conditions; therefore, it is involved in adaptive pathways to better fulfill tissue needs in a disturbed environment. SIRT1 overexpression or activation is protective in neurodegenerative diseases. Its role in acute nervous system injury, such as brain ischemia, is emerging, but whether SIRT1 activation improves stroke outcome is still a matter of controversy. In the present review, we will document present knowledge about the contribution of SIRT1 in death/survival in cell and animal models of brain ischemia and discuss whether SIRT1 could be a valuable target for therapeutic intervention in human stroke.

An epidemiological analysis of characteristics of 1092 major trauma in patients the central area of Jiangmen

Objective To provide some reference for making prevention and intervention measures by investigating the epidemiologic characteristics and influencing factors of major trauma in Jiangmen.Methods The epidemiologic data of 1092 major trauma patients who had visited our hospital during the period of November 1,2005 to October 31,2009 were retrospectively analyzed.Results 1092 patients met the criteria for this study.There were 825 male and 267 female, aged 34.65 ± 18.19 years.Age distribution:3 cases of death in the children group of 98,61 cases of death in the young group of 735,14 cases of death in the middle-aged group of 190, 7 cases of death in the elderly group of 69.Causes of trauma:road or traffic injury in 635 patients,injuries by a fall in 98 patients,injuries by sharp materials in 56 patients,injury by machines in 65 patients,bum in 118 patients,fall injury in 61 patients,and other causes in 59 patients.According to the anatomic points partition method,separate zone A injuries in 581 cases ( 53.21％ ),40 cases of death ( 47.06％ ); a separate B injuries in 64 cases ( 5.86％ ),3 cases of death ( 3.53％ ); a separate C injuries in 151 cases ( 13.83％ ),7 cases of death ( 8.24％ ); multiple zone 296 injured cases ( 27.11％ ),and 35 cases were dead (41.18％ ).Wound types:blunt trauma in 836 cases,with a survival of 773 and death of 63； penetrating injury in 256 cases,with a survival of 234 and death of 22.Death cases:68 male and 17 female,with blunt injury in 63 and penetrating injury in 22.The average age of death was 37.27 ± 17.68 years.Treatment and outcomes:849 cases of surgical treatment and 243 cases of conservative treatment.1007 patients survived and 85 were dead.The main causes of death of acute central nervous system injury and uncontrol bleeding.Conclusions Occurrence of major trauma has some regularity in age,occupation,place of the accidence,causes of trauma,and injured parts of the body.The preventive and intervention measures for the populatiou at highrisk can effectively reduce the morbidity and mortality. Key words: Major trauma; Epidemiology

Posictal neurogenic pulmonary edema secondary to acute poisoning by organochlorine pesticide in an adolescent suicide attempt

We reported the case of an adolescent, without neurological background, who attempted suicide by organochlorine pesticide ingestion. The acute intoxication was expressed as a convulsive status epilepticus followed by an acute neurogenic pulmonary edema with rapid recovery within 48 hours. The diagnosis of neurogenic pulmonary edema in pediatrics, and particulary after a seizure, is unusual and often an exclusion one. Its evolution tends to be favorable, but can be fatal if it is not recognized and treated early. An acute nervous system injury associated with signs and symptoms of respiratory failure suggests the diagnosis. Other causes of pulmonary edema must be ruled out in order to avoid evaluation and treatment mistakes.

Proton magnetic resonance spectroscopy improves outcome prediction in perinatal CNS insults.

Prediction of neurologic outcome is difficult in neonates with acute nervous system injury. Previous studies using proton magnetic resonance spectroscopy ((1)H-MRS) have been used to predict short-term neurologic outcome in neonates with a variety of neurologic insults. We were interested in determining the effectiveness of combining clinical evaluation and spectroscopy obtained at the time of injury in predicting neurologic outcome at 24 months. We studied 33 neonates with acute central nervous system injury, 5.8+/-3.7 days of injury, owing to hypoxic-ischemic encephalopathy. Neonates were assessed using clinical variables (initial arterial pH, initial blood glucose, Sarnat score, electroencephalography) and spectroscopy (NAA/Cho, NAA/Cre, Cho/Cre, and lactate). Neonates were divided into two outcome groups: good/moderate and poor. Differences between the groups were assessed using chi(2) and t-test analyses. We analyzed the best predictors of outcome using discriminant analysis and calculated sensitivity, specificity, positive, and negative predictive values for each variable independently and in combination. There were significant differences between the good/moderate and poor outcome for the Sarnat score, EEG, lactate, and NAA/Cho. Spectroscopy combined with clinical variables improved sensitivity, but not specificity for predicting outcome. The presence of lactate had the best individual predictive value. Combination of the clinical with the MRS variables had the highest predictive value. Proton magnetic resonance spectroscopy done early after injury improves the ability to predict neurologic outcome at 24 months of age.