Progress in brain research
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Human death is a unitary phenomenon that physicians can determine in two ways: (1) showing the irreversible cessation of all brain clinical functions; or (2) showing the permanent cessation of circulatory and respiratory functions. Over the last 40 years the determination of human death using neurological tests ("brain death") has become an accepted practice throughout the world but has remained controversial within academic circles. Brain death has a rigorous biophilosophical basis by defining death as the irreversible loss of the critical functions of the organism as a whole. ⋯ Among physicians, the area of greatest controversy in death determination now is the use of circulatory-respiratory tests, particularly as applied to organ donation after circulatory death. Circulatory-respiratory tests are valid only because they produce destruction of the whole brain, the criterion of death. Clarifying the distinction between the permanent and irreversible cessation of circulatory and respiratory functions is essential to understanding the use of these tests, and explains why death determination in organ donation after circulatory death does not violate the dead donor rule.
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The natural history of recovery from brain injury typically consists of a period of impaired consciousness, a subsequent period of confusion and amnesia, followed by a period of post-confusional recovery of function. Patients with more severe injuries may have more prolonged episodes of unconsciousness or minimal consciousness and may not fully evolve through this continuum of recovery. There is limited information on the course of recovery and long-term outcome of patients with prolonged unconsciousness, particularly those with extended periods in the minimally conscious state. Further, patients with impaired consciousness are frequently denied access to hospital-based rehabilitation services because of uncertain prognosis and a perceived lack of benefit from rehabilitative interventions. ⋯ Patients in VS whose transition to MCS occurred within 8 weeks of onset are likely to continue recovering to higher levels of functioning, a substantial proportion to household independence, and productive pursuits. Patients with TBI are more likely to progress than patients with nonTBI, though significant improvement in the nonTBI group is still possible. Active, higher intensity, rehabilitation should be strongly considered for patients with severely impaired consciousness after brain injury, especially for patients with TBI who have signs of progression to the MCS.
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The search for a "magic bullet" drug targeting a single receptor for the treatment of stroke or traumatic brain injury (TBI) has failed thus far for a variety of reasons. The pathophysiology of ischemic brain injury and TBI involves a number of mechanisms leading to neuronal injury, including excitotoxicity, free radical damage, inflammation, necrosis, and apoptosis. Brain injury also triggers auto-protective mechanisms, including the up-regulation of anti-inflammatory cytokines and endogenous antioxidants. ⋯ Laboratories around the world have shown that progesterone and allopregnanolone act through numerous metabolic and physiological pathways that can affect the injury response in many different tissues and organ systems. Furthermore, progesterone is a natural hormone, synthesized in both males and females, that can act as a pro-drug for other metabolites with their own distinct mode of action in CNS repair. These properties make progesterone a unique and compelling natural agent to consider for testing in clinical trial for CNS injuries including TBI and stroke.
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Review
The use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of spasticity.
Spasticity is a common disorder in patients with injury of the brain and spinal cord, especially in patients affected by multiple sclerosis (MS). In MS, spasticity is a major cause of long-term disability, it significantly impacts daily activities and quality of life and is only partially influenced by traditional spasmolytic drugs. ⋯ The H reflex is a reliable electrophysiologic measure of the stretch reflex, and has been used in previous studies to test the effects of rTMS of the motor cortex on spinal circuitry. Based on these premises, originating from physiological studies in normal subjects, some studies have demonstrated that rTMS of the leg motor cortex can be beneficial in the management of spasticity by enhancing corticospinal tract excitability and reducing H reflex amplitude.
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Spinal cord injury (SCI) is a serious clinical problem for which no suitable therapeutic strategies have been worked out so far. Recent studies suggest that the SCI and its pathophysiological responses could be altered by systemic exposure to nanoparticles. Thus, SCI when made in animals intoxicated with engineered nanoparticles from metals or silica dust worsened the outcome. ⋯ This indicates that nanoparticles depending on the exposure and its usage could induce both neurotoxicity and neuroprotection. This review discusses the potential adverse or therapeutic utilities of nanoparticles in SCI largely based on our own investigations. In addition, possible mechanisms of nanoparticle-induced exacerbation of cord pathology or enhanced neuroprotection following nanodrug delivery is described in light of recently available data in this rapidly emerging field of nanoneurosciences.