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Muscle-fiber compartmentalization in cat splenius muscles.

Splenius is a structurally complex muscle that is supplied by nerves from four cervical segments. We have examined the architectural organization of extrafusal fibers in splenius by microdissecting muscles stained "en bloc" with gold chloride. We also analyzed the distribution of motor units supplied from different cervical segments using the glycogen-depletion technique. Microdissections show that the fiber architecture of splenius is different in medial and lateral muscle parts. In medial splenius, muscle fascicles run uninterrupted from the muscle origin to insertion, while in lateral splenius, separate compartments of muscle fascicles are linked in series by two tendinous inscriptions. In muscle fascicles longer than 2.0 cm, many extrafusal fibers do not run the whole length of the fascicle. Instead, these fibers end intramuscularly by tapering to a fine strand that is closely adherent to adjacent extrafusal fibers. Less than 1% of extrafusal fibers in splenius exceeds 3.0 cm in length. Experiments using glycogen depletion showed that nerves from different spinal segments innervate different muscle regions. Nerves from C1 supply muscle fibers in a small rostromedial zone. Nerves from C2-C4 have motor domains that extend from the medial to the lateral muscle edge and are arranged in series. In lateral splenius, the motor domains are separated by tendinous inscriptions. In medial splenius, where no inscriptions are present, the motor domains of adjacent segmental nerves have overlapping boundaries due to the extensive interdigitation of motor units supplied from different segmental nerves. A single muscle fascicle in medial splenius is commonly composed of two sets of fibers supplied by adjacent segments that are distributed at opposite ends of the fascicle and interdigitate in midregions of the fascicle. The in-series compartmentalization of splenius has important implications for its motor control. To secure effective muscle shortening or tension development, central mechanisms may be required to coordinate the recruitment of in-series motor units. The presence of many short fibers with intramuscular insertions leads us to question how contractile forces are developed and transmitted in splenius and other mammalian muscles that are composed of short, in-series fibers.

Animals↗

Regularity analysis in a compartmental model of chopper units in the anteroventral cochlear nucleus.

1. We investigate the discharge patterns of chopper units in the anteroventral cochlear nucleus (AVCN) by developing an equivalent cylinder compartmental model of AVCN stellate cells, which are the sources of the chopper response pattern. The model consists of a passive dendritic tree connected to somatic and axonal compartments with voltage-sensitive channels. Synaptic inputs to the model are simulated auditory nerve fiber responses to best-frequency tones. 2. We adjust the anatomic and electrical parameters of the model to agree with available intracellular data from stellate cells in the AVCN of the mouse and the cat and compare the response of the model to injected current with responses recorded in vitro. The model shows approximately linear current-voltage characteristics for small hyperpolarizing currents. The model's input resistance and the time course of its response to hyperpolarizing current applied at the soma are comparable with those measured from stellate cells in vitro. In response to sustained depolarizing current, the model fires repetitively with nearly perfect regularity, a property also observed in vitro. 3. Auditory nerve inputs to the cell are modeled as deadtime-modified Poisson processes with a multiexponential adaptation in the Poisson rate. We are able to adjust the number, rate, and location of excitatory and inhibitory inputs to the model and succeed in simulating chopper response patterns seen in vivo. 4. Chopper units exhibit a variety of regularity and adaptation patterns in response to tone stimuli. Physiological data from brain slice experiments and experiments in vivo imply that this heterogeneity is primarily due to differences in input configurations. By systematically varying the number and position of excitatory and inhibitory inputs, we can simulate a range of chopper response patterns. 5. We quantify the regularity of the model's response using the coefficient of variation (CV) of the interspike interval. We find that the CV decreases, i.e., the regularity increases, as the number of converging inputs or their distance from the soma increases. The regularity of the output is more sensitive to the number of converging inputs than to their location on the dendritic tree. The statistics of the first spike latency (FSL) are also sensitive to the configuration of excitatory inputs. The mean and minimum FSL are more sensitive to the electrotonic distance of the inputs from the soma than to the number of inputs, whereas the standard deviation of the FSL is highly dependent on the number of converging inputs and is nearly independent of their location.(ABSTRACT TRUNCATED AT 400 WORDS)

Axons↗

Estimating the electrotonic structure of neurons with compartmental models.

1. A procedure based on compartmental modeling called the "constrained inverse computation" was developed for estimating the electrotonic structure of neurons. With the constrained inverse computation, a set of N electrotonic parameters are estimated iteratively with use of a Newton-Raphson algorithm given values of N parameters that can be measured or estimated from experimental data. 2. The constrained inverse computation is illustrated by several applications to the basic example of a neuron represented as one cylinder coupled to a soma. The number of unknown parameters estimated was different (ranging from 2 to 6) when different sets of constraints were chosen. The unknowns were chosen from the following: dendritic membrane resistivity Rmd, soma membrane resistivity Rms, intracellular resistivity Ri, membrane capacity Cm, dendritic membrane area AD, soma membrane area As, electrotonic length L, and resistivity-free length, rfl (rfl = 2l/d1/2 where l and d are length and diameter of the cylinder). The values of the unknown parameters were estimated from the values of an equal number of known parameters, which were chosen from the following: the time constants and coefficients of a voltage transient tau 0, tau 1, ..., C0, C1, ..., voltage-clamp time constants tau vc1, tau vc2, ..., and input resistance RN. Note that initially, morphological data were treated as unknown, rather than known. 3. When complete morphology was not known, parameters from voltage and current transients, combined with the input resistance were not sufficient to completely specify the electrotonic structure of the neuron. For a neuron represented as a cylinder coupled to a soma, there were an infinite number of combinations of Rmd, Rms, Ri, Cm, AS, AD, and L that could be fitted to the same voltage and current transients and input resistance. 4. One reason for the nonuniqueness when complete morphology was not specified is that the Ri estimate is intrinsically bound to the morphology. Ri enters the inverse computation only in the calculation of the electrotonic length of a compartment. The electrotonic length of a compartment is l[4 Ri/(dRmd)]1/2, where l and d are the length and diameter of the compartment. Without complete morphology, the inverse computation cannot distinguish between a change in d or l and a change in Ri. Even when morphology is known, the accuracy of the Ri estimate obtained by any fitting procedure is affected by systematic errors in length and diameter measurements (i.e., tissue shrinkage); the Ri estimate is inversely proportional to the length measurement and proportional to the square root of the diameter measurement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Substrate-induced nuclear export and peripheral compartmentalization of hepatic glucokinase correlates with glycogen deposition.

Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopy and quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60 min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface.

Active Transport, Cell Nucleus↗

Cellular and subcellular compartmentation of creatine kinase in brain.

Creatine kinase (CK) catalyzes a reversible transphosphorylation reaction that is believed to play a crucial role in the maintenance and channeling of high energy phosphate in tissues with high energy demands. In rat brain development, cytosolic (nonmitochondrial) CK levels increase rapidly during the peak period of myelination and remain high in the adult. The cellular compartmentation of CK was investigated through the use of primary cultures of neurons, oligodendrocytes and astrocytes. The CK activity in cultured oligodendrocytes, which expressed both enzymatic and immunocytochemical markers of myelin, was the highest of the cell types examined and comparable to levels measured in whole adult brain; these observations suggest a role for CK in myelinogenesis. We found that low density, dividing astrocyte cultures also exhibited high B-CK (brain isoenzyme of CK) immunoreactivity, with the nuclear CK staining being especially intense. We studied these cultured astrocytes in more detail with respect to their intense nuclear CK immunoreactivity. Optical sections of astrocyte nuclei taken with a confocal microscope show that the high B-CK present is actually contained within the nucleus, with a nucleoplasmic distribution that does not co-localize with DNA or RNA. To ascertain whether the high nuclear B-CK in proliferating astrocytes correlated with ongoing cell division, we conducted experiments with confluent, nondividing cultures. These results show that both CK enzyme activity and immunoreactivity are high in the nucleus of proliferating astrocytes, and significantly reduced in the nucleus of quiescent, nondividing astrocytes. The high level of CK protein and activity in the nucleus of proliferating astrocytes suggests a role for CK in cell division/nuclear function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes.

Studies from several groups have provided evidence that glutamate and glutamine are metabolized in different compartments in astrocytes. In the present study we measured the rates of 14CO2 production from U-[14C]glutamate and U-[14C]glutamine, and utilized both substrate competition experiments and the transaminase inhibitor aminooxyacetic acid (AOAA) to obtain more information about the compartmentation of these substrates in cultured rat brain astrocytes. The rates of oxidation of 1 mM glutamine and glutamate were 26.4 +/- 1.4 and 63.0 +/- 7.4 nmol/h/mg protein, respectively. The addition of 1 mM glutamate decreased the rate of oxidation of glutamine to 26.3% of the control rate, demonstrating that glutamate can effectively compete with the oxidation of glutamine by astrocytes. In contrast, the addition of 1 mM glutamine had little or no effect on the rate of oxidation of glutamate by astrocytes, demonstrating that the glutamate produced intracellularly from exogenous glutamine does not dilute the glutamate taken up from the media. The addition of 5 mM AOAA decreased the rate of 14CO2 production from glutamine to 29.2% of the control rate, consistent with earlier studies by our group. The addition of 5 mM AOAA decreased the rate of oxidation of concentrations of glutamate < or = 0.1 mM by approximately 50%, but decreased the oxidation of 0.5-1 mM glutamate by only approximately 20%, demonstrating that a substantial portion of glutamate enters the tricarboxylic acid (TCA) cycle via glutamate dehydrogenase (GDH) rather than transamination, and that as the concentration of glutamate increases the relative proportion entering the TCA cycle via GDH also increases. To determine if the presence of an amino group acceptor (i.e. a ketoacid) would increase the rate of metabolism of glutamate, pyruvate was added in some experiments. Addition of 1 mM pyruvate increased the rate of oxidation of glutamate, and the increase was inhibited by AOAA, consistent with enhanced entry of glutamate into the TCA cycle via transamination in the presence of pyruvate. Enzymatic studies showed that pyruvate increased the activity of mitochondrial aspartate aminotransferase (AAT). Overall, the data demonstrate that glutamate formed intracellularly from glutamine enters the TCA cycle primarily via transamination, but does not enter the same TCA cycle compartment as glutamate taken up from the extracellular milieu. In contrast, extracellular glutamate enters the TCA cycle in astrocytes via both transamination and GDH, and can compete with, or dilute, the oxidation of glutamate produced intracellularly from glutamine.

Aminooxyacetic Acid↗

Acute peroneal compartmental syndrome. Report of a case.

Among the compartmental syndromes the necrosis of peroneal muscles is unusual. We report a case in which the swelling of peroneal muscle causes a compression of the common peroneal nerve below the peroneal head. A disturbance of both the motility and sensibility of the deep and superficial peroneal nerve is present with different pathogenesis. In fact, EMG suggested a muscular damage of the peroneal compartment and a denervation of the pretibial muscle. Interfascicular neurolysis along the peroneal nerve was performed to decompress the common and the deep peroneal nerve. A recovery in the territory of the tibialis anterior deep peroneal nerve confirmed the different mechanisms of paralysis.

Adult↗

A compartmentalized, organ-cultured hypothalamo-neurohypophysial system for the study of vasopressin release.

In the compartmentalized hypothalamo-neurohypophysial system ( CHNS ), a portion of medial basal hypothalamus (HT) containing the supraoptic nuclei (SON) and the neurohypophysis (PP) were organ-cultured in separate compartments. The intact axonal projections from SON to PP passed through a hole in a fluid-tight barrier which separated the two compartments. When properly sealed, the leak rate from one side to the other is less than 1%/24 h and the only connection between the 2 compartments is axonal. This system had relatively stable basal vasopressin (VP) release rates from both HT and PP for up to 72 h in culture. Basal neurohypophysial VP release rate was unchanged during two successive 1-hour periods on any given day. Physiological responsiveness was confirmed by osmotic challenge. When HT osmolality was changed by +/- 15 mosm, VP release from PP was appropriately and significantly increased or decreased. Equivalent changes in PP side osmolality had no effect on VP release. After 72 h in culture, the VP content of neural lobes from CHNS explants was more than double that of lobes which were severed from HT prior to culture. Finally, the presence of numerous VP neurophysin-containing cells in 72-hour cultured explants was demonstrated by immunocytochemistry. This system will be useful to localize sites of action for agents affecting VP release to either HT and/or PP.

Animals↗

Effect of cholinergic antagonists on basal and osmotically stimulated vasopressin release in compartmentalized hypothalamo-neurohypophysial explants.

The effects of cholinergic antagonists on vasopressin (VP) release were studied in an organ-cultured, compartmentalized, rat hypothalamo-neurohypophysial system which allows selective application of stimuli to either hypothalamus or pituitary without disrupting axonal connections. Release of vasopressin from the neurohypophysis was measured by radioimmunoassay. Hexamethonium (10(-5) M) and atropine (5 X 10(-5) M) were tested both alone and in combination with hypothalamic osmotic stimulation (+ 15 mosm/kg H2O). In hypothalamus, neither hexamethonium nor atropine had any effect on basal VP release from pituitary. Hexamethonium, but not atropine, prevented the increase in VP release produced by increased osmolality of the hypothalamus side culture medium. In contrast, hexamethonium had no effect when applied to pituitary side, whereas atropine suppressed both basal and osmotically stimulated VP release. Atropine had no effect on basal or KCl-induced VP release in detached neural lobes. Acetylcholine (Ach) (10(-5) M) to pituitary plus simultaneous, hypothalamic stimulation (osmotic or 10(-5) M Ach) did not increase VP release above the hypothalamic stimulus alone. The results support a role for a hypothalamic excitatory nicotinic mechanism in osmoregulation. The presence of a muscarinic mechanism affecting VP release in pituitary was reconfirmed, but the data did not support the hypothesis that Ach stimulates VP release in pituitary by a presynaptic facilitatory mechanism.

Acetylcholine↗

The development of molecular compartmentation in the cerebellar cortex.

The cerebellum is subdivided into hundreds of discrete modules defined by their connectivity and molecular signatures. Cerebellar compartmentation arises very early in development through the formation of multiple populations of chemically distinct Purkinje cells that migrate in a coordinated fashion to form parasagittal bands of cells. Different Purkinje cell bands are then innervated by discrete subpopulations of cerebellar afferents. Because of its stereotyped and strikingly beautiful organization the cerebellum is an excellent model in which to explore genetic/epigenetic aspects of pattern formation in the central nervous system.

Animals↗

Blood amino acid compartmentalization during pregnancy and lactation in the rat.

The blood amino acid compartmentalization during pregnancy and lactation of the rat have been studied. Cellular amino acid levels are similar to those of the plasmatic fraction. Important generalized decreases are detected on days 12 and 21 of the pregnancy; Glu + Gln, Ala and essential and semiessential amino acids being the most affected. During lactation, after a transient phase on day 1 after delivery, there is a generalized increase in blood levels, especially in the plasma fraction, that affects the whole essential values. The different patterns shown by amino acids during pregnancy and lactation confirm that the measurement of plasmatic levels underestimates the actual capacity of whole blood to transport amino acids.

Amino Acids↗

Compartmental analysis of the plasma clearance of tetrabromsulphthalein and dibromsulphthalein in the normal dog and in patients with liver disease.

A comparison has been made of the plasma clearances of the anionic dye analogues, tetrabromsulphthalein (BSP) and dibromsulphthalein (dBSP), analysed by means of a two-compartmental model. In the normal conscious dog all three transport rate constants and initial and steady state plasma clearances were greater with dBSP than BSP. On the other hand the equivalent liver volume (ELV) and storage capacity were lower with dBSP. In patients with various hepatic disorders dBSP values were greater than those obtained with BSP apart from rate constant b (liver to plasma). Patients with advanced liver impairment in general exhibited lower hepatic uptake, clearance and storage of both dyes compared to patients with mild forms of liver disease. The ratio of ELV values for BSP and dBSP appeared to be related to overall hepatic function, with ratios greater than 1 in the normal dogs and less than 1 in the patients.

Adult↗

Development of compartmental models in stable-isotope experiments: application to lipid metabolism.

Kinetic experiments are of great importance in lipid research because they further the understanding of lipid metabolism in vivo and help to explain the physiopathology of lipid disorders in humans. At present, due to species specificity, no valid animal model can efficiently replace a study in humans to explore lipid metabolism, and the use of radioactive tracers is restricted in humans. Thus, stable-isotope tracer kinetic studies have become an important component of research programs to achieve in humans a quantitative understanding of the dynamics of metabolic processes in vivo. The aim of this review is to describe the practical aspects of compartmental model development in stable-isotope experiments. The recent development of computer hardware and modeling software has dramatically facilitated the task of the modeler in his or her calculations. In the current review, we show that the model may be considered an integral component of the experimental design and that model development must obey strict rules to provide a rigorous solution. The main difficulties of model development in tracer experiments, such as experiment design, model identifiability, data expression, comparison of models, or tracer recycling, are presented with extensive references. We have paid particular attention to kinetic modeling in stable-isotope experiments because they have shown the greatest development in recent years.

Animals↗

Compartmentalization of water in human atherosclerotic lesions. Changes in distribution and exclusion volumes for plasma macromolecules.

High concentrations of LDL and other plasma macromolecules are present in normal aortic intima and early proliferative atherosclerotic lesions that have not yet accumulated lipid. Their compartmentalization within the tissue water was estimated from the concentrations of low density lipoprotein (LDL), alpha 2-macroglobulin (alpha 2-M), and albumin in interstitial fluid and adjacent intimal tissue. Interstitial fluid was collected on filter paper inserted into natural strip planes in the intima; macromolecules in interstitial fluid and tissue were assayed by rocket immunoelectrophoresis directly from the papers or tissue. From their concentrations in interstitial fluid and total tissue water, the fractional and absolute volumes in which they were distributed (distribution volume) or from which they were excluded (exclusion volume) were calculated for each macromolecule. Compared with normal intima, the distribution volume increased by 60% and the exclusion volume by 95% in early gelatinous lesions; exclusion volume fraction was linearly related to molecular mass. In more advanced lesions, there was disproportionate exclusion of LDL and alpha 2-M. Their distribution volumes decreased and their concentrations in interstitial fluid increased; the concentration showed a significant inverse relation with distribution volume (regression coefficient, b = -0.53, p less than 0.01). Redistribution of tissue water may concentrate LDL in interstitial fluid, and contribute to its extracellular deposition.

Adult↗

Compartmentalized phosphodiesterase-2 activity blunts beta-adrenergic cardiac inotropy via an NO/cGMP-dependent pathway.

beta-Adrenergic signaling via cAMP generation and PKA activation mediates the positive inotropic effect of catecholamines on heart cells. Given the large diversity of protein kinase A targets within cardiac cells, a precisely regulated and confined activity of such signaling pathway is essential for specificity of response. Phosphodiesterases (PDEs) are the only route for degrading cAMP and are thus poised to regulate intracellular cAMP gradients. Their spatial confinement to discrete compartments and functional coupling to individual receptors provides an efficient way to control local [cAMP]i in a stimulus-specific manner. By performing real-time imaging of cyclic nucleotides in living ventriculocytes we identify a prominent role of PDE2 in selectively shaping the cAMP response to catecholamines via a pathway involving beta3-adrenergic receptors, NO generation and cGMP production. In cardiac myocytes, PDE2, being tightly coupled to the pool of adenylyl cyclases activated by beta-adrenergic receptor stimulation, coordinates cGMP and cAMP signaling in a novel feedback control loop of the beta-adrenergic pathway. In this, activation of beta3-adrenergic receptors counteracts cAMP generation obtained via stimulation of beta1/beta2-adrenoceptors. Our study illustrates the key role of compartmentalized PDE2 in the control of catecholamine-generated cAMP and furthers our understanding of localized cAMP signaling.

Adenine↗

Compartmentalization of adriamycin and daunomycin in cultured chick cardiac myocytes. Effects on synthesis of contractile and cytoplasmic proteins.

The affinity of two anthracycline antineoplastics [( 14C]adriamycin and [14C]daunomycin) for cultured embryonic chick heart cells was determined by measuring their uptake, compartmentalization into subcellular fractions, and effects on the synthesis of cytoplasmic and cytoskeletal proteins. Both drugs, at micromolar concentrations, were readily uptaken by myocytes and found to be concentrated in a light-buoyant-density fraction containing no lysosomes. Nuclear 14C drug content accounted for 20-25% of the drug incorporated. Binding of adriamycin was saturable within 90 minutes of drug exposure, and the uptake of [14C]adriamycin was inhibited 50% by verapamil and adenosine triphosphate. Uptake of [14C]daunomycin was not influenced by these compounds. Cytosolic and contractile protein synthesis measured by [35S]methionine incorporation into proteins was blocked 70% overall in each fraction after 6 hours of incubation with 2 microM adriamycin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography and quantitative densitometry, revealed that actin synthesis was the least affected of the major proteins. Cardiac myocytes incubated for short periods of time with 2 microM adriamycin revealed subtle cytoplasmic changes in their organelles with the appearance of clear zones of cytoplasm containing short unorganized microfilaments. The deleterious effects of anthracyclines in heart cells are manifested early by rapid drug incorporation into myocytes and inhibition of cytoplasmic protein synthesis.

Animals↗

Adenine nucleotide metabolism and compartmentalization in isolated adult rat heart cells.

The metabolism and intracellular compartmentalization of adenine nucleotides in a preparation of adult rat heart myocytes showing good morphology, viability, and tolerance to calcium ion has been examined by high performance liquid chromatography. These myocytes contain an average of 23 nmol adenine nucleotide per milligram protein which is about 60% of the adenine nucleotide content of intact rat heart tissue. The loss of adenine nucleotide occurs during the incubation and washing steps that increase the yield of viable cells, rather than during the collagenase perfusion. An analysis of cellular compartments shows that the adenine nucleotide of the cell consists of 17 nmol adenine nucleotide in the cytosol, 5 nmol in the mitochondria, and 1.3 nmol adenosine diphosphate bound to myofibrils per milligram cell protein. Myocytes lose both adenosine triphosphate and adenine nucleotide when incubated anaerobically in the absence of glucose, and the lost adenine nucleotide can be accounted for as increased inosine, adenosine, and inosine monophosphate. Myocytes that contain less than 0.1 nmol of cytosol adenosine triphosphate per milligram cell protein maintain an intact sarcolemma, but are unable to carry out anaerobic glycolysis. Reoxygenation of anaerobic cells results in restoration of energy charge and a net resynthesis of about 2 nmol adenine nucleotide per milligram protein. Adenosine and inosine monophosphate decrease on reaeration of anaerobic cells, whereas inosine levels increase. When iodoacetate is added to block glycolysis, the decline in adenine nucleotide and production of inosine monophosphate are accelerated and there is no resynthesis of adenine nucleotide when anaerobic cells are reoxygenated . Large accumulations of inosine monophosphate are also seen in myocytes treated with an uncoupler of oxidative phosphorylation.

Adenine Nucleotides↗

Flow and compartmental weight in relation to the cours of stroke.

Using a scintillation camera system, hemispheric and regional cerebral blood flow was measured repeatedly during the course after a stroke. In 20 patients who improved clinically mean hemispheric and regional flow and relative weight of rapidly perfused compartment increased, while these values decreased in 15 patients, on an average, whose clinical condition deteriorated or did not change. The changes of flow and relative weight were significantly different between the two groups. Futhermore, the relationship between changes in clinical condition, scored according to a rating scale, and changes in flow and compartmental weight was proved by significant Spearman rank correlation coefficients. In six cases hyperperfused areas in locations of disturbed neurological function were observed; these areas were found to be ischemic at measurements done early and late in the cours after the stroke. This type of hyperperfusion was related to beneficial prognosis. The results indicate a shift of tissue form fast to slowly cleared compartment after a cerebrovascular attack. If tissue morphology is not entirely destroyed, recovery might occur; this results in an increase of recorded weight of rapidly clearing compartments, which correlates to the clinical course.

Adolescent↗