Brain deficits

Acetylcholine Precursors. Early efforts to treat dementia using cholinomimetics focused on choline [62-49-7] (12) supplement therapy (Fig. 3). This therapy, analogous to L-dopa [59-92-7] therapy for Parkinson s disease, is based on the hypothesis that increasing the levels of choline in the brain bolsters acetylcholine (ACh) synthesis and thereby reverses deficits in cholinergic function. In addition, because choline is a precursor of phosphatidylcholine as well as ACh, its supplementation may be neuroprotective in conditions of choline deficit (104). 

S100B Developmental brain dysfunction, learning and memory deficits... 

Lakshmana MK, Raju TR. 1994. Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance. Toxicology 91(2) 139-50. 

Berman NE, Marcario JK, Yong C et al (1999) Microglial activation and neurological symptoms in the SIV model of NeuroAIDS association of MHC-II and MMP-9 expression with behavioral deficits and evoked potential changes. Neurobiol Dis 6 486 98 Biber K, Zuurman MW, Dijkstra IM et al (2002) Chemokines in the brain neuroimmunology and beyond. Curr Opin Pharmacol 2 63-68... 

There is a definite trend of bidirectional cross-talk between opioid and chemokine receptors in the central nervous system. In vitro, as well as in vivo studies, have shown desensitization of CXCR4 by MOR and thus prevent the neuroprotective action of this chemokine. Although the precise molecular mechanism underlying this cross-talk is still under investigation, based on the evidences in literature several possible pathways can be expected to act independently or in concert and lead to the deficit of CXCR4 function. Our studies have shown that p opioids can increase the brain levels of FHC which can subsequently block CXCR4 signaling. Eurther studies... 

With modest impairment of blood flow, this mechanism allows for preservation of oxidative metabolism without alteration in electrical function. However, when CPP and therefore CBF are sufficiently low, OEF reaches a maximum and cannot increase further. Brain tissue ceases to function electrically, resulting in a neurologic deficit. Microvascular collapse occurs, and CBV falls. If the oxygen supply falls low enough, the tissue dies. Of critical clinical importance is the observation that the amount of time it takes for tissue to suffer irreversible damage is inversely related to the severity of the ischemic insult. Tissue that is completely deprived of blood will die within a few minutes, but less severely hypoperfused tissue may survive for many hours, and may be saved by timely thrombolysis that restores perfusion, or perhaps by another therapeutic intervention. 

Veltkamp R, Warner DS, Domoki F, Brinkhous AD, Toole JF, Busija DW. Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats. Brain Res 2000 853 68-73. 

The proposal that NO or its reactant products mediate toxicity in the brain remains controversial in part because of the use of non-selective agents such as those listed above that block NO formation in neuronal, glial, and vascular compartments. Nevertheless, a major area of research has been into the potential role of NO in neuronal excitotoxicity. Functional deficits following cerebral ischaemia are consistently reduced by blockers of NOS and in mutant mice deficient in NOS activity, infarct volumes were significantly smaller one to three days after cerebral artery occlusion, and the neurological deficits were less than those in normal mice. Changes in blood flow or vascular anatomy did not account for these differences. By contrast, infarct size in the mutant became larger... 

Geyer, MA, Swerdlow, NR, Mansbach, RS and Braff, DL (1990) Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res. Bull. 25 485-498. 

Drawing all this evidence together, Schildkraut (1965) concluded that depression was caused by a functional deficit of noradrenergic transmission in the brain. He also thought that the rebound depression and fatigue, which are experienced after the arousing effects of amphetamine have worn off, were due to depletion of neuronal stores of noradrenaline. However, Schildkraut made a clear distinction between the effects of antidepressants and the arousal induced by amphetamine, describing the latter as stimulation and excitement . To this day, there is controversy over whether or not amphetamine has a beneficial effect in depression. 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

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