The thermodynamic brain

Apart from its complex functionality, the brain is a robust thermodynamic machine; the tissue metabolic rate is high and it is thermally shielded by a skull. Therefore, if there is no high-volume blood flow to cool and stabilize the brain temperature, the possibility of unstable behavior seems to be high. Inflowing arterial blood is normally cooler than the brain tissue temperature, and outflowing venous blood is normally warmer than arterial blood but cooler than the brain tissue. Brain blood flow can thus be understood as a cooler for the brain. Pros and cons of clinical measurement, with clear indication for a multimodal monitoring approach, are discussed along with a brief review of basic facts known about temperature, cerebral blood flow and volume, intracranial pressure, and compartmental compliances of the brain.A large quantity of experimental works, sometimes with conflicting conclusions, have been published about the regulation of core temperature and brain temperature. Bedside clinical studies, however, are not that common. Measurement of cerebral blood flow in comparison with core body temperature in traumatic brain injury (TBI) patients, as presented in a recent issue of Critical Care by Stretti and colleagues, is therefore worth commendation [1].Cooling the body to protect the brain and preserve life may sound like something from science fiction. However, cooling seems to have very real beneficial effects. Some of our friends in the animal kingdom can withstand remarkable physiologic insults, at least when they are cold. For example, Spermophilus tridecemlineatus (ground squirrels) can tolerate 90% reductions in cerebral perfusion without any neurologic deficit, provided their temperature is reduced to 10°C during hibernation [2]. In fact, cooling has been used as a therapy in medicine for decades [3]. Since its inception, enthusiasm for cooling has waxed and waned in the domains of cardiopulmonary bypass, cardiac arrest, stroke, and TBI [4]. Because temperature has the potential to alter cerebral metabolism, blood flow and intracranial pressure (ICP), therapeutic cooling has been proffered as a management strategy after TBI. However, clinical trials in TBI have not been conclusive to date [5,6], prompting a new large-scale multicenter European trial [7]. In any case, clinical trials usually differ from scientific procedures because they provide pragmatic answers for clinicians (if conclusive) but often not for scientists. The need to establish a link between clinical utility and scientific rationale forces us to return to simple questions such as that posed by Stretti and colleagues: what are the brain hemodynamic effects of temperature changes?The basic tenants underpinning therapeutic cooling in TBI are related to the fundamental relationship between temperature and the rate of biochemical reactions common to all species [8], and the effect of temperature on ICP. The brain may be particularly sensitive to changes in temperature for two reasons: the brain is highly metabolically active; and, due to the rigid cranium, temperature-induced changes in metabolism and cerebral blood volume can result in changes in ICP. The ICP itself is governed by the volume of the various compartments in the skull; namely, the vascular, parenchymal, and cerebrospinal fluid (CSF) compartments. The question then arises as to which component of ICP temperature affects.The vascular component is the obvious choice because decreasing temperature increases vascular tone in the small pial vessels [9], and perhaps even in the basal arteries [10]. Aside from altering the vascular component of ICP, it is also possible (and as yet unknown) that the CSF or parenchymal compartments are altered – for example, by altering CSF production or reabsorption, or by affecting the osmotic composition of the parenchymal interstitium. Separating such components will be difficult to achieve experimentally and especially clinically.Stretti and colleagues used transcranial Doppler (TCD) ultrasonography during alteration in body temperature after TBI in an attempt to further our understanding of the cerebral hemodynamic consequences of cooling. TCD is a stethoscope for the brain, and its bedside use in several scenarios should be more widespread. The advantages of TCD measurements on arrival at neurocritical care, to make a quick assessment and decide about the first few hours’ management strategy, have been highlighted recently [11]. TCD measures blood flow velocity, not volumetric flow, and because it has a pulsatile component can (and should) be analyzed with pulse waveform signal processing methodology. In addition, combining TCD velocity measures with arterial blood pressure and cerebral perfusion pressure can provide further insight into cerebral hemodynamics by describing the autoregulation, vascular compliance, resistance, time constant, wall tension, critical closing pressure, and other parameters.In the current study, the relationships between core body temperature and cerebral hemodynamics were studied in two groups of TBI patients: those with a fever who were subsequently cooled (defervescence group); and those who were hypothermic who were warmed to normothermia (rewarming group) [1]. The mean flow velocity observed in the rewarming group is nearly twice lower than that in the defervescence group. This disproportion remains apparent even if the upper temperature in rewarmed patients was close to the lower temperature in the defervescence group. This observation may suggest that there is no one universal temperature–cerebral blood flow relationship, and other physiological variables obviously play a role. The authors report that with lower temperature we see lower mean arterial pressure and lower TCD pulsatility index. This is a novel finding. The pulsatility index is theoretically proportional to the pulsation of blood pressure and (nonlinearly) to a product of cerebrovascular resistance and arterial compartmental compliance multiplied by the heart rate, but inversely proportional to cerebral perfusion pressure [12]. We still know little about vascular resistance and compliance when temperature varies, and cerebral perfusion pressure is reported to stay constant at least in the defervescence group; therefore, it is possible that the lowering of arterial blood pressure pulse amplitude is responsible for the reduced pulsatility index with lower temperature.In conclusion, Stretti and colleagues touch complex and still poorly chartered phenomena. Because of the multifactorial interactions between brain injury, temperature control, cerebral blood flow, and autoregulation, the answer to all questions is impossible within an observational study design based on a limited number of cases. Nevertheless, this paper opens a thought-provoking discussion and, we hope, will stimulate further clinical research in the area of the thermodynamic brain.     

The dynamic fetal brain

PURPOSE: To evaluate fetuses with normal intracranial anatomy in the second trimester that became abnormal in the third trimester. METHODS: We sonographically examined 6 fetuses with a normal second-trimester head sonogram that presented later in pregnancy with an abnormal head sonogram. RESULTS: Four categories of intracranial pathology were depicted: obstructive hydrocephalus, intraventricular intracranial hemorrhage, non-intraventricular intracranial hemorrhage, and porencephaly. CONCLUSIONS: Despite a normal midtrimester intracranial examination, evaluation of the fetal intracranial contents should be undertaken in subsequent sonographic examinations, because significant pathology can develop spontaneously.     

The disappearing brain lesions

A 66-year-old Caucasian female presented with headaches. MRI brain revealed white matter changes confined to her hindbrain that completely resolved within two weeks. Various case reports have been published attributing multiple causes for reversible posterior leukoencephalopathy syndrome (RPLE), a condition that this patient had. No obvious causes except for mild hypertension were responsible for her presentation. Even in absence of reported causes, diagnosis of RPLE should be entertained in right clinical scenario and suggestive radiologic findings. Such patients should be closely followed since on rare occasional the condition may be irreversible.     

The pathophysiology of shock brain

Shock brain is becoming more recognized as a distinct clinical problem. However, in order to effectively prevent and treat it, the clinician must have a firm grasp of the metabolic requirements and oxygen supply and demand of the normal brain. In addition, it is useful to understand how various types of shock compare and contrast in their ability to injure the brain. In this way, health professionals will be able to base assessment findings and therapies on sound physiologic principles, and thus hopefully improve patient outcomes.     

The phenomenon of chemo brain

During and following chemotherapy, some patients experience difficulties with memory, attention, and other aspects of cognitive function. This constellation of deficits commonly is referred to as chemo brain. Although the phenomenon is not understood completely, it is assuming greater significance as cancer survival improves. Return to prediagnosis levels of domestic, employment, and academic activity is expected in most survivors. Advances in basic, imaging, and clinical sciences are beginning to unravel pathophysiologic mechanisms and develop neuroprotective strategies. Pharmacologic options are borrowed from diverse diseases, including attention-deficit/hyperactivity disorder and neurodegenerative diseases. Conventional therapies soon may find new applications; for example, recent preclinical data suggest that erythropoietin may have some neuroprotective abilities, which may positively affect patients experiencing chemo brain. A collaborative model is bringing together international specialists interested in unraveling the mysteries of the phenomenon and developing management strategies to attenuate its effects. This article will review the clinical features of chemo brain as well as a working hypothesis regarding pathophysiology. The potential and emerging interventions that can be used by oncology nurses to assist patients and their families to cope with this enigmatic dysfunction will be discussed.     

The brain and brown fat

Abstract

Brown adipose tissue (BAT) is a specialized organ responsible for thermogenesis, a process required for maintaining body temperature. BAT is regulated by the sympathetic nervous system (SNS), which activates lipolysis and mitochondrial uncoupling in brown adipocytes. For many years, BAT was considered to be important only in small mammals and newborn humans, but recent data have shown that BAT is also functional in adult humans. On the basis of this evidence, extensive research has been focused on BAT function, where new molecules, such as irisin and bone morphogenetic proteins, particularly BMP7 and BMP8B, as well as novel central factors and new regulatory mechanisms, such as orexins and the canonical ventomedial nucleus of the hypothalamus (VMH) AMP- activated protein kinase (AMPK)–SNS–BAT axis, have been discovered and emerged as potential drug targets to combat obesity. In this review we provide an overview of the complex central regulation of BAT and how different neuronal cell populations co-ordinately work to maintain energy homeostasis.     

重症颅脑损伤后弥漫性脑肿胀的影像诊断

目的探讨脑外伤所致的弥漫性脑肿胀临床特点、发病机制及影像类型。方法分析48例脑外伤引起的弥漫性脑肿胀的临床及影像图像资料。结果48例脑外伤引起的弥漫性脑肿胀中有33例合并脑挫裂伤（包括12例脑弥漫性轴索损伤，1例合并大脑基底节区梗死）、31例合并硬膜外、硬膜下或脑内血肿、27例合并颅骨骨折、10例合并蛛网膜下腔出血。弥漫性脑肿胀影像表现：①双侧大脑半球弥漫性肿胀，双侧脑室、脑池对称性缩小或消失，中线结构无移位；②一侧大脑半球弥漫性肿胀，同侧脑室、脑池受压缩小或消失，中线结构向对侧移位；③可伴蛛网膜下腔出血或皮层下小灶性出血；④脑实质CT值可低于、略高于或等于正常脑组织。结论颅脑外伤导致下丘脑和脑干血管运动中枢受损引起脑血管扩张是广泛弥漫性脑肿胀的发病机制之一，弥漫性脑肿胀有4种CT表现，非出血性弥漫性脑肿胀可由脑缺氧后再灌注所致。     

The life history of brain dopamine

Neurochemical studies in Parkinson's disease have greatly contributed to the understanding of the neurobiology of the meso-telencephalic dopamine (DA) system; in addition, these studies have significantly influenced our concepts regarding the general principles of brain function. The primary role of DA in striatal function can be seen in its ability to initiate complex patterns of motor activity. The nigro-striatal DA system shows in the face of partial damage an extraordinarily high degree of plasticity, i.e. capacity for functional compensation. The two most important mechanisms of plasticity of the nigro-striatal DA system are: compensatory activation of the presynaptic remaining DA neurons (through increase in DA turnover); and increase in the number of postsynaptic DA receptors. The DA loss which occurs during normal ageing is not of sufficient magnitude to cause clinically overt Parkinson's disease. On the other hand, the observations pertaining to the Parkinsonian syndrome produced by NMPTP suggest the participation of environmental factors in the aetiology of idiopathic Parkinson's disease. The remarkable results of nigral cell transplants into the striatum of animals with experimental "parkinsonism", as well as the high therapeutic efficacy of DA substitution in patients with Parkinson's disease point toward a neurohumoral, rather than neurotransmitter, function of brain DA.