Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

Physiology of Microglia

Applications of the Morris water maze in the study of learning and memory.

Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. In recent years, patterns of injury have been changing, with more injuries, particularly contusions, occurring in older patients. Blast injuries have been identified as a novel entity with specific characteristics. Traditional approaches to the classification of clinical severity are the subject of debate owing to the widespread policy of early sedation and ventilation in more severely injured patients, and are being supplemented with structural and functional neuroimaging. Basic science research has greatly advanced our knowledge of the mechanisms involved in secondary damage, creating opportunities for medical intervention and targeted therapies; however, translating this research into patient benefit remains a challenge. Clinical management has become much more structured and evidence based since the publication of guidelines covering many aspects of care. In this Review, we summarise new developments and current knowledge and controversies, focusing on moderate and severe TBI in adults. Suggestions are provided for the way forward, with an emphasis on epidemiological monitoring, trauma organisation, and approaches to management.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70164-9.pdf

Moderate and severe traumatic brain injury in adults.

In childhood, traumatic brain injury (TBI) poses the unique challenges of an injury to a developing brain and the dynamic pattern of recovery over time, inflicted TBI and its medicolegal ramifications. The mechanisms of injury vary with age, as do the mechanisms that lead to the primary brain injury. As it is common, and is the leading cause of death and disability in the USA and Canada, prevention is the key, and we may need increased legislation to facilitate this. Despite its prevalence, there is an almost urgent need for research to help guide the optimal management and improve outcomes. Indeed, contrary to common belief, children with severe TBI have a worse outcome and many of the consequences present in teenage years or later. The treatment needs, therefore, to be multifaceted and starts at the scene of the injury and extends into the home and school. In order to do this, the care needs to be multidisciplinary from specialists with a specific interest in TBI and to involve the family, and will often span many decades.

Traumatic brain injury.

All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga­ nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be­ come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti­ tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere­ brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1981.18

Cell Damage in the Brain: A Speculative Synthesis

The purpose of the present experiment was to examine the effectiveness of a modified rotarod test in detecting motor deficits following mild and moderate central fluid percussion brain injury. In addition, this investigation compared the performance of the rotarod task with two other commonly used measures of motor function after brain injury (beam-balance and beam-walking latencies). Rats were either injured with a mild (n = 14) or moderate (n = 8) level of fluid percussion injury or were surgically prepared but not injured (n = 8). All rats were assessed on all tasks for 5 days following their respective treatments. Results revealed that both the mild and moderate injury levels produced significant deficits in the ability of the animals to perform the rotarod task. Performance on the beam-balance and beam-walking tasks were not significantly impaired at the mild injury level. It was only at the moderate injury level that the beam-balance and beam-walking tasks detected deficits in motor perform...

The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.

These experiments examined the effects of moderate hypothermia on mortality and neurological deficits observed after experimental traumatic brain injury (TBI) in the rat. Brain temperature was measured continuously in all experiments by intraparenchymal probes. Brain cooling was induced by partial immersion (skin protected by a plastic barrier) in a water bath (0 degrees C) under general anesthesia (1.5% halothane/70% nitrous oxide/30% oxygen). In experiment I, we examined the effects of moderate hypothermia induced prior to injury on mortality following fluid percussion TBI. Rats were cooled to 36 degrees C (n = 16), 33 degrees C (n = 17), or 30 degrees C (n = 11) prior to injury and maintained at their target temperature for 1 h after injury. There was a significant (p less than 0.04) reduction in mortality by a brain temperature of 30 degrees C. The mortality rate at 36 degrees C was 37.5%, at 33 degrees C was 41%, and at 30 degrees C was 9.1%. In experiment II, we examined the effects of moderate hypothermia or hyperthermia initiated after TBI on long-term behavioral deficits. Rats were cooled to 36 degrees C (n = 10), 33 degrees C (n = 10), or 30 degrees C (n = 10) or warmed to 38 degrees C (n = 10) or 40 degrees C (n = 12) starting at 5 min after injury and maintained at their target temperatures for 1 h. Hypothermia-treated rats had significantly less beam-walking, beam-balance, and body weight loss deficits compared to normothermic (38 degrees C) rats. The greatest protection was observed in the 30 degrees C hypothermia group.(ABSTRACT TRUNCATED AT 250 WORDS)

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.1991.13

Marked Protection by Moderate Hypothermia after Experimental Traumatic Brain Injury

Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat.

Inflicted Childhood Neurotrauma: New Insight into The Detection, Pathobiology, Prevention, and Treatment of Our Youngest Patients with Traumatic Brain Injury

Traumatic brain injury produces significant cognitive deficits in humans. This experiment used a controlled cortical impact model of experimental brain injury to examine the effects of brain injury on spatial learning and memory using the Morris water maze task. Rats (n = 8) were injured at a moderate level of cortical impact injury (6 m/sec, 1.5-2.0 mm deformation). Eight additional rats served as a sham-injured control group. Morris water maze performance was assessed on days 11-15 and 30-34 following injury. Results revealed that brain-injured rats exhibited significant deficits (p less than 0.05) in maze performance at both testing intervals. Since the Morris water maze task is particularly sensitive to hippocampal dysfunction, the results of the present experiment support the hypothesis that the hippocampus is preferentially vulnerable to damage following traumatic brain injury. These results demonstrate that controlled cortical impact brain injury produces enduring cognitive deficits analogous to those observed after human brain injury.

Larry W. Jenkins

Papers

The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.

Marked Protection by Moderate Hypothermia after Experimental Traumatic Brain Injury

Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat.

Inflicted Childhood Neurotrauma: New Insight into The Detection, Pathobiology, Prevention, and Treatment of Our Youngest Patients with Traumatic Brain Injury

Cognitive deficits following traumatic brain injury produced by controlled cortical impact.