Cerebral threshold

Astmp J, Siesjo BK, Symon L. Thresholds in cerebral ischemia - the ischemic penumbra. 

Nordstrom CH. 2003. Assessment of critical thresholds for cerebral perfusion pressure performing bedside monitoring of cerebral energy metabolism. Neurosurg Focus... 

Ethosuximide has an important effect on Ca2+ currents, reducing the low-threshold (T-type) current. This effect is seen at therapeutically relevant concentrations in thalamic neurons. The T-type calcium currents are thought to provide a pacemaker current in thalamic neurons responsible for generating the rhythmic cortical discharge of an absence attack. Inhibition of this current could therefore account for the specific therapeutic action of ethosuximide. Ethosuximide also inhibits Na+/K+ ATPase, depresses the cerebral metabolic rate, and inhibits GABA aminotransferase. However, none of these actions are seen at therapeutic concentrations. 

Threshold fields were around 10 and 56 V/m in air for chick and cat tissues, respectively, but sensitivity decreased at 100 V/m. Thus, calcium binding in chick and cat cerebral tissue exhibited frequency and amplitude windows in responses to these extremely weak fields (Figure 2B). 

Especially in models of transient cerebral ischemia, apoptotic cell death has been observed after 3-7 days post insult in selected brain regions in which basal energy metabolism has been preserved (Chen et al. 1997 Du et al. 1996). In the meantime, molecular switches have been identified that gate different populations of neurons with regard to the type of cell death they eventually undergo (Nicotera 2003). However, there is little doubt that in animal stroke the vast majority of cells would die from necrosis or, alternatively, secondary energy failure even in the presence of a pro-apop-totic genetic balance. The concept of thresholds of cerebral blood flow (CBF) for various functions of brain parenchyma (see below) explains why the infarct core suffers from pan-necrosis whereas the peri-infarct border in which function is suppressed, but structure initially preserved (the so-called ischemic penumbra), may show apoptotic cell death or a combination of both. 

Fig. 4.4. Bar graph of viability thresholds of cerebral blood flow for a variety of functions and metabolites. Note that selective neuronal loss occurs at consistently higher flow values than overt infarction. CMRG, cerebral metabolic rate of glucose PCr, phosphocreatine ATP, adenosine triphosphate. [Adapted and reproduced with permission from Hossmann (1994)]...

Hata R, Maeda K, Hermann D, Mies G, Hossmann KA (2000) Evolution of brain infarction after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 20 937-946 HeissW-D (1983) Flow thresholds to functional and morphological damage of brain tissue. Stroke 14 329-331 Heiss W-D, Rosner G (1983) Functional recovery of cortical neurons as related to degree and duration of ischemia. Ann Neurol 14 294-301... 

Review of literature. Cerebrovasc Dis 1 2-15 Hossmann K-A (1994) Viability thresholds and the penumbra of focal ischemia. Ann Neurol 36 557-565 Hossmann KA, Hoehn-Berlage M (1995) Diffusion and perfusion MR imaging of cerebral ischemia. Cerebrovasc Brain Metab Rev 7 187-217... 

Fig. 7.2. Relationship between relative (rADC) and cerebral blood flow (CBF). ADC drops to below normal at CBF values around 15-24 ml/min/100 g, as shown in a pixel-wise comparison between diffusion and perfusion imaging in acute stroke patients. A lower threshold (15 ml/min/100 g) was found for patients imaged earlier (up to 4 h ) compared to the value (24 ml/min/100 g) of those patients imaged between 4.5 and 6.5 h ( ).The data show that the ADC threshold increases with time. [Reproduced with permission from Lin et al. (2003)]...

Naritomi H, Sasaki M, Kanashiro M, Kitani M, Sawada T (1988) Flow thresholds for cerebral energy disturbance and Na+ pump failure as studied by in vivo 31P and 23Na nuclear magnetic resonance spectroscopy. J. Cereb. Blood Flow Metab 8 16-23... 

Paschen W, Mies G, Hossmann KA (1992) Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in ger-bils. Exp.Neurol 117 325-333... 

Baron JC (2001). Perfusion thresholds in human cerebral ischemia historical perspective and therapeutic implications. Cerebrovascular Diseases 11 2-8... 

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