Changes in circulating inflammatory cells and the relationship to secondary brain injury in patients with craniocerebral injury★

BACKGROUND:Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING: A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences...     

Changes in circulating inflammatory cells and the relationship to secondary brain injury in patients with craniocerebral injury★

BACKGROUND: Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING: A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS: Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS: WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES: The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS: WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury (P < 0.01). These measures negatively correlated to the Glasgow coma scale (r = -0.657, -0.541, respectively, P < 0.05). In patients with Glasgow coma sale < 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 (P < 0.05). Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size (P < 0.05). CONCLUSION: WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale. Key Words: craniocerebral injury; inflammatory cells; secondary brain injury     

Looking forward: An impaired ability in patients with schizophrenia?

When two visual stimuli occur within 8 to 17ms of one another, subjects cannot tell they are asynchronous, yet recent results show they are not processed as simultaneous. Two spatially separate squares were presented at an interval ranging from 0 to 92ms and remained on the screen until subjects responded. Subjects pressed a right or left response key according to the judged simultaneity/asynchrony of the stimuli. We evaluated the Simon effect, i.e., the tendency to press the key on the same side as the stimulus. We found an effect even when the squares were displayed on opposite sides of the screen, with their onsets separated by less than 20ms. Controls were biased towards the last stimulus, whereas patients with schizophrenia were biased towards the first. We investigate here whether the results are related to spatial or temporal processing. Using the same paradigm, we explored the impact of spatial grouping by comparing connected vs. unconnected stimuli and manipulating the predictability of the second stimulus location. We tested different groups of mildly symptomatic patients and matched controls in two studies. Under 20ms, when stimuli were connected and the 2nd square location was predictable, patients tended to press the key to the side of the 1st square, whereas controls displayed the opposite tendency. The results suggest that controls put more emphasis on the last occurring event, but not patients with schizophrenia. This impairment is observed when spatial difficulties are removed, suggesting it is related to time rather than space.     

Neurological disease: are systems approaches the way forward?

Most neurological diseases are multifactorial diseases, where environmental conditions combine with genetic background or somatic mutations to trigger a pathological state. In the case of Parkinson's Disease and Schizophrenia, recent research revealed that susceptibility genes coded for proteins involved at different steps of specific metabolic networks and cellular processes. Comprehension of the pathology of those diseases is therefore very likely to benefit from Systems approaches. This is also true of their symptomatology, affecting neurological systems at molecular, cellular, and microcircuit levels.     

The predictive brain state: timing deficiency in traumatic brain injury?

Attention and memory deficits observed in traumatic brain injury (TBI) are postulated to result from the shearing of white matter connections between the prefrontal cortex, parietal lobe, and cerebellum that are critical in the generation, maintenance, and precise timing of anticipatory neural activity. These fiber tracts are part of a neural network that generates predictions of future states and events, processes that are required for optimal performance on attention and working memory tasks. The authors discuss the role of this anticipatory neural system for understanding the varied symptoms and potential rehabilitation interventions for TBI. Preparatory neural activity normally allows the efficient integration of sensory information with goal-based representations. It is postulated that an impairment in the generation of this activity in traumatic brain injury (TBI) leads to performance variability as the brain shifts from a predictive to reactive mode. This dysfunction may constitute a fundamental defect in TBI as well as other attention disorders, causing working memory deficits, distractibility, a loss of goal-oriented behavior, and decreased awareness.     

The injury response in the term newborn brain: can we neuroprotect?

PURPOSE OF REVIEW: Perinatal hypoxia-ischemia is responsible for significant morbidity and mortality in term infants. The developing brain is uniquely vulnerable to hypoxic-ischemic injury, with a complex evolution of injury that affords opportunities for intervention, yet potentially jeopardizes normal maturational processes. RECENT FINDINGS: Data published over the past year have provided insights into the evolution of injury, and have suggested a greater role for oxidants and inflammatory mediators. SUMMARY: The search for ideal neuroprotective agents and techniques for timely injury detection is actively progressing and has led to advances in our understanding of pathogenesis.     

Neuroprotective agents in brain injury: a partial failure?

Brain injury leads to inflammation, stress, and cell death. Neurons are more susceptible to injury than astrocytes, as they have limited antioxidant capacity, and rely heavily on their metabolic coupling with astrocytes to combat oxidative stress. Both normally and after brain injury, astrocytes support neurons by providing antioxidant protection, substrates for neuronal metabolism, and glutamate clearance. Although astrocytes are generally more resilient than neurons after injury, severe damage also results in astrocyte dysfunction, leading to increased neuronal death. This mini review provides a very insightful and brief overview on a few examples of promising neuroprotective compounds targeting astrocyte function, with specific attention on how these treatments alter astrocyte response or viability, and how this may be critical for neuronal survival following brain injury.     

Can nimodipine prevent ischaemic reperfusion injury in the rat brain?

Abstract

Reperfusion injury is a pathophysiological entity distinct from the primary ischaemic injury; the oxygen arriving with blood recirculation, although necessary for alleviating the ischaemic status, may be harmful and provoke additional injury in the already damaged tissue. This study aims to analyse whether nimodipine reduces cerebral dysfunction after transient global cerebral ischaemia, using our previously described experimental model’ which permits the impregnation of cerebral tissue during the periods of ischaemia and reperfusion. Some aspects of this study contribute to our understanding of the reperfusion injury concept Three groups of rats were used. Animals in Croup 1 (n = 13) served as normal controls for neurophysiological recordings. Rats in Croups 2 (n = 7) and 3 (n = 7) were subjected to global cerebral ischaemia and either isotonic saline (Croup 2) or nimodipine solution (Group 3; 40 μg/kg) was intra-arterially injected through the external carotid artery during ischaemia and reperfusion and distributed to the circle of Willis. Seventy-two hours after global cerebral ischaemia somatosensory evoked potentials were evaluated and P1 wave latency was used to compare the three groups of animals. The peak onset of this wave was 8.13 ± 1.5 msec, 18.63 ± 3.1 msec and 13.17 ± 2 msec for Croups 1, 2 and 3 respectively. P1 latency was significantly higher in Group 2 than in Groups 1 and 3 (p < 0.01). Histopathological findings showed that the level of injury in the hippocampus and striatum in Group 3 was more limited than in Group 2, although no statistical significance could be found. There was correlation between neurophysiological findings and the neuropathological damage observed in the striatum for Groups 2 and 3. It is concluded that the intra-arterial injection of nimodipine lessens brain damage caused by transient global cerebral ischaemia in rats. [Neurol Res 1993; 15: 395-400]     

Is therapeutic hypothermia beneficial for pediatric patients with traumatic brain injury? A meta-analysis

Purpose

Hypothermia therapy shows its unique potential for reducing mortality in animal study and improving neurologic outcome in patients with traumatic brain injury. However, therapeutic hypothermia for pediatric traumatic brain injury remains a controversial issue. To determine the effectiveness and safety of hypothermia treatment for pediatric traumatic brain injury patients, we conducted this meta-analysis.

Patients and methods

We analyzed the data from MEDLINE, Pubmed, EMBASE, and Cochrane Library by electronic searching. No limitation of language was selected for analysis. We extracted the mortality and adverse events from the published trials.

Results

Six clinical trials and 366 pediatric patients met our inclusion criteria. Pediatric patients with traumatic brain injury treated with hypothermia had more unfavorable outcome than those in the normothermia group (RR 1.73, 95 % CI 1.06 to 2.84), and this increased risk is statistically significant. Patients with therapeutic hypothermia are slightly likely to be induced by cardiac arrhythmia, and the likelihood is also significant (RR 2.57, 95 % CI 1.01 to 6.54). Risk of pneumonia has no statistical difference between normothermia and hypothermia arms (RR 0.90, 95 % CI 0.73 to 1.12). Two of the included trials have reported their detail randomization assignment.

Conclusions

Hypothermia may slightly increase the risk of mortality in children with traumatic brain injury and the ratio of cardiac arrhythmia after this hypothermia therapy is slightly higher than that in normothermia groups. In the future, more randomized controlled trials and multicenter studies on the mechanism of therapeutic hypothermia are required.     

Cerebral blood volume alterations in the perilesional areas in the rat brain after traumatic brain injury��comparison with behavioral outcome

In the traumatic brain injury (TBI) the initial impact causes both primary injury, and launches secondary injury cascades. One consequence, and a factor that may contribute to these secondary changes and functional outcome, is altered hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after severe controlled cortical impact injury were characterized to assess their interrelations with motor function impairment. Magnetic resonance imaging (MRI) was performed 1, 2, 4 h, and 1, 2, 3, 4, 7, and 14 days after TBI to quantify CBV and water diffusion. Neuroscore test was conducted before, and 2, 7, and 14 days after the TBI. We found distinct temporal profile of CBV in the perilesional area, hippocampus, and in the primary lesion. In all regions, the first response was drop of CBV. Perifocal CBV was reduced for over 4 days thereafter gradually recovering. After the initial drop, the hippocampal CBV was increased for 2 weeks. Neuroscore demonstrated severely impaired motor functions 2 days after injury (33% decrease), which then slowly recovered in 2 weeks. This recovery parallelled the recovery of perifocal CBV. CBV MRI can detect cerebrovascular pathophysiology after TBI in the vulnerable perilesional area, which seems to potentially associate with time course of sensory-motor deficit.