Brain animal models

According to the amyloid hypothesis, the A 3 peptide plays a critical role in the pathogenesis of Alzheimer s disease [1]. Major forms of A 3 produced encompass 38, 40 or 42 residues. A 342 is more prone to aggregation than A 340 and in animal models an increased A[342/ A (340 ratio results in amyloid plaque pathology even when total A 3 levels are reduced [4]. The generation of A 3 is a normal process and A 3 is present in the brains and body fluids of humans throughout life. Neuronal... 

S100A1 is the most abundant in the myocardium but is also expressed in brain and other tissues. S100A1 was found to stimulate Ca2+-induced Ca2+-release (CICR) in skeletal muscle terminal cisternae. In the presence of nanomolar Ca2+-concentrations, S100A1 binds to the ryanodine receptor increasing its channel open probability, and was shown to enhance SR Ca2+-release and contractile performance. Several animal models (over expressing S100A1 or S100A1-deficient mice) have... 

Zhu Y, Antony J et al (2006) CD8-t lymphocyte-mediated injury of dorsal root ganghon neurons during lentiviras infection CD 154-dependent ceU contact neurotoxicity. J Neurosci 26(13) 3396-3403 Zhu Y, Antony JM et al (2007) Didanosine causes sensory neuropathy in an HIV/AIDS animal model impaired mitochondrial and neurotrophic factor gene expression. Brain 130(Pt 8) 2011-2023... 

Tran PB, Ren D, Veldhouse TJ, Miller RJ (2004) Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J Neurosci Res 76 20-34 Tran PB, Banisadr G, Ren D, Chenn A, Miller RJ (2007) Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain. J Comp Neurol 500 1007-1033 U eyler N, Sommer C (2008) Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett 437 194-198... 

Tris-hydroxymethyl-aminomethane (THAM) has been evaluated in ischemic stroke to reduce mass effect and ICP. It acts as a bulfer, neutralizing acidosis on a local level, including in the brain parenchyma. It has been studied in animal models of stroke, showing an effect in reducing the size of and swelling from cerebral infarction. To date, however, THAM has not been studied in a controlled fashion in humans with ischemic stroke. 

Attempts to find the cause(s) of depression have adopted two main approaches. One is to look for the neurobiological basis of depression in human subjects and animal models of this condition. The second is to investigate the pharmacology of established antidepressant agents to see whether they consistently augment some, and ideally the same, neurobiological targets in the brain. 

HU-210 is (8.1) among the most potent cannabinoids known. Its enantiomer HU-211 (8.2) does not bind to the cannabinoid receptor and lacks psychotropic side effects (as long as optical purity is guaranteed). In animal models it shows analgesic and antiemetic activity. It also shows neuroprotec-tive effects after brain injury and was tested in humans as anti-traiuna agent, where it did not meet the expectations in a clinical phase III trial. 

Ceballos-Picot, I., Nicole, A., Briand, P., Grimber, G., Delacourte, A., Defossez, A., Javoy-Agid, F., Lafon, M., Blouin, J.L. and Sinet, P.M. (1991). Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice animal model of gene dosage effects in Down s syndrome. Brain Res, 552, 198-214. 

Carvediol is a vasodilator with beta-adrenergic antagonist activity. It has cardioprotective activity in animal models. The antioxidant effect of carvediol was compared with five other beta blockers in iron-initiated lipid peroxidation, where it inhibited TBARs formation and protected membrane-bound tocopherol in rat brain homogenate (Yue et al., 1992a). The ortJ <)-substituted phenoxylethyl-amine is responsible for the improved antioxidant activity. 

A series of dihydrodibenzoxepines, represented by AJ3941, was tested in animal models of global ischaemia and hypoxia, and found to be protective. AJ3941 is an inhibitor of lipid peroxidation (Kurakawa etal., 1991). A novel quinazoline fumarate (KB56666, was found to inhibit lipid peroxidation in rat brain homogenates and isolated mitochondria. In a rat focal stroke model, KE56666 prevented brain oedema and neuronal damage in the ischaemic zone (Hara etal., 1991). 

Robinson, T.E., and Becker, J.B. Enduring changes in brain and behavior produced by chronic amphetamine administration A review and evaluation of animal models of amphetamine psychosis. Brain Res 11 157-198, 1986. 

BP 2.94) or (5) (Sch 50971) induce significant increases of slow-wave sleep or induce sedation in animal models [10, 33]. Potent and selective brain-penetrating H3 agonists could provide a new therapeutic option for the treatment of insomnia. 

V. ANIMAL MODELS OF BRAIN DEPOSITION OF INSOLUBLE PROTEINS... 

Walker LC. Animal models of cerebral beta-amyloid angiopathy. Brain Res Brain Res Rev 1997 25 70-84. 

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