Brain anoxia

Half the epilepsy cases are secondary to trauma, brain anoxia, infection, lesions, or cerebrovascular disorder (CVA) [commonly referred to as a stroke]. Cause of the other half is unknown (idiophatic). Seventy-five percent of persons with seizures had their first seizure before 18 years of age. There are various... 

McLean A Jr, Cardenas DD, Burgess D and Gamzu E (1991). Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia. Brain Injury, 5, 375-380. 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

A variety of different types of tissue preparation are used to study neurosecretion and synaptic transmission. A classical preparation is the frog NMJ (discussed below). The brain slice has been used for many years for biochemical studies of CNS metabolism and is a useful preparation for electrophysiological studies of synaptic transmission in the CNS. Slices can be oriented to maintain the local neuronal circuitry and can be thin, 0.3 mm, to minimize anoxia. The transverse hippocampal slice is widely used as an electrophysiological preparation to study synaptic plasticity (see Ch. 53). Primary cultures of neurons from selected CNS areas and sympathetic ganglia are also frequently used. They permit excellent visual identification of individual neurons and control of the extracellular milieu, but the normal neuronal connections are disrupted. 

Innovative methodologies for in vivo microdialysis in immature subjects have facilitated research in multiple areas. Clinically driven experimentation on neonatal anoxia, hypoxia, or ischemia indicates that perinatal manipulations of oxygen and blood flow result in acute and chronic disruptions of neurotransmission and transmitter turnover (Chen et al., 1997 Nakajima et al, 1999 Ogasawara et al., 1999). Recently, a role for toxic free radicals in brain damage induced by prenatal infection was also delineated by in vivo microdialysis in rat pups (Cambonie et al, 2000, 2004). More subtle neonatal manipulations, such as maternal separation or periodic neonatal isolation, coupled with subsequent in... 

Ogasawara M, Nakajima W, Ishida A, Takada G. 1999. Striatal perfusion of indomethacin attenuates dopamine increase in immature rat brain e3q>osed to anoxia an in vivo microdialysis study. Brain Res 842(2) 487-490. 

Some substances, such as carbon monoxide and barbiturates, can deprive brain cells of oxygen or glucose - they produce anoxia - with potentially serious consequences for gray matter. Other substances, such as lead, hexachlorophene, and the antitubercular drug isoniazid, are capable of causing loss of myelin, a coating or sheath for the axon and dendrites that extend from the central unit (cell body) of neurons. Demyelination can occur in either the CNS or PNS. 

Carbon monoxide Interferes with oxygen transport by blood, resulting in the reduction of oxygen supply to the heart (chronic anoxia), heart and brain damage, impaired perception... 

The toxic effect is known as histotoxic hypoxia. Cyanide also directly stimulates chemoreceptors, causing hyperpnea. Lack of ATP will affect all cells, but heart muscle and brain are particularly susceptible. Therefore, cardiac arrythmias and other changes often occur, resulting in circulatory failure and delayed tissue ischemic anoxia. Death is usually due to respiratory arrest resulting from damage to the CNS, as the nerve cells of the respiratory control center are particularly sensitive to hypoxia. The susceptibility of the brain to pathological damage may reflect the lower concentration of cytochrome oxidase in white matter. 

The isolated cell preparation is an important system for the in vivo NMR spectro-scopist in terms of gaining a better understanding of the NMR spectra obtained in the intact animal. For example, H spectra of isolated neuronal and glial cells may help us to determine the contribution that these two cell types make to the H spectra of intact brain. The response of tumor cells to anoxia, ischemia, etc. may aid interpretation of the spectra obtained from similar cells in a solid tumor in an animal or human patient following certain clinical interventions, such as chemotherapy or alteration of tumor perfusion with vasoactive drugs. 

Sykova E, Svoboda J, Polak J, Chvatal A (1994) Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat. J Cereb Blood Flow Metab 14 301-311 Van der Toorn A, Dijkhuizen RM, Tulleken CA, Nicolay K (1996a) Diffusion of metabolites in normal and ischemic rat brain measured by localized 1H MRS. Magn Reson Med 36 914-922... 

Most instructive is what happens to the same processes in 02-limited turtle liver cells. Under conditions of total anoxia, the ATP demand of protein turnover drops to less than 10% of normoxic rates urea biosynthesis drops to essentially zero, as does the biosynthesis of glucose (not unexpectedly, because a major role of the liver under anoxic conditions is to supply glucose for the rest of the body). Although the ATP requirements of the Na+-K+-ATPase are also drastically reduced, the suppression in percentage terms is less than for overall ATP turnover. As a result, under anoxic conditions, the Na+ pump becomes the cell s dominant energy sink, accounting for up to 75% of the ATP demand of the cell (Buck and Hochachka, 1993). In turtle brain these adjustments occur along with a measurable decrease in Na+-K+-... 

Hylland, P., S. Milton, M. Pek, G.E. Nilsson, and P.L. Lutz (1997). Brain Na+/K+-ATPase activity in two anoxia tolerant vertebrates crucian carp and freshwater turtle. Neurosci. Lett. 235 89-92. 

Lutz, P.L. and L. Manuel (1999). Maintenance of adenosine A1 receptor function during long-term anoxia in the turtle brain. Am. J. Physiol. 276 R633-R636. 

Acetylcholine was first injected intravenously as a therapeutic convulsant in 1939, in the justified expectation that the fits would be less liable to cause fractures than those following therapeutic leptazol convulsions. Recovery rates of up to 80% were claimed in various psychotic conditions. Enthusiasm began to wane however when it was shown that the fits were due to anoxia resulting from cardiac arrest and not to pharmacological effects on the brain. ... 

The essential element, hypoperfusion of vital organs, is present whatever the cause, whether pump failure (myocardial infarction), maldistribution of blood (septic shock) or loss of total intravascular volume (bleeding or increased permeability of vessels damaged by bacterial cell products, bums or anoxia). Fimction of vital organs, brain (consciousness, respiration) and kidney (urine formation) are clinical indicators of adequacy of perfusion of these organs. 

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