Biomedical subjects

M D Habgood

Publications and source records attributed to M D Habgood.

24 records · Page 2Linked to original sources

PubMed1992

A developmentally regulated blood-cerebrospinal fluid transfer mechanism for albumin in immature rats.

1. The transfer of albumin between the blood and the cerebrospinal fluid (CSF) has been investigated in neonatal (3 days old) and juvenile (20 days old) rats. At both stages of postnatal development, all of the albumin present in the CSF can be accounted for by transfer from the blood. Thus it is unlikely that in situ synthesis of albumin contributes to the naturally high levels of albumin in CSF in the developing brain. 2. The high concentration of albumin in CSF of the neonatal rat brain cannot be accounted for solely by diffusion from the blood. In the 3-day-old rat, only about one quarter of the albumin in CSF enters by diffusion from the blood, whilst the remainder appears to be transported into the CSF by a specific mechanism which can discriminate between different species of albumin. The specific transport component of albumin transfer between the blood and the CSF appears to be developmentally regulated and is not apparent in 20-day-old rats. 3. Chemical modification of albumin resulting in either an increase or a decrease in electrophoretic mobility (at pH 7.4), significantly reduces blood-CSF transfer of albumin in 3-day-old rats, but has little effect in the 20-day-old rat. Thus overall molecular charge does not appear to be an important feature of the species-specific blood-CSF albumin transport mechanism in neonatal rats.

Age Factors↗

PubMed1991

Cerebral blood flow in the anaesthetized immature sheep fetus and the response to hypercapnia.

Regional cerebral blood flow (CBF) has been measured in eight anaesthetized, exteriorized, fetal sheep between 58 and 62 days gestation; four were controls, four were hypercapnic (PaCO2 = 78 +/- 5 mmHg, mean +/- S.E.M.). Blood flow values were calculated from quantitative autoradiography following the infusion of [14C]iodoantipyrine into a cannulated fetal placental vein, for the cerebellum, medulla, and five layers of the developing neocortex: cortical plate (CP), subplate zone (SP), intermediate zone (IZ), subventricular zone (SV), and the ventricular zone (VZ). The highest control CBF rates were recorded in the cortical plate (49.3 +/- 7.4 ml min-1 (100 g)-1, mean +/- S.E.M., posterior cortex) and in the ventricular zone (40.5 +/- 4.8, posterior cortex), which at this stage of development are the regions of greatest cell density. The lowest CBF rates were recorded in the subplate zone (23.8 +/- 6.8, anterior cortex) and in the intermediate zone (23.4 +/- 7.6, anterior cortex), which are the regions of lowest cell density. Experimentally induced hypercapnia increased CBF in all brain regions and enhanced the regional pattern of flow. The results provide evidence that CBF in the immature fetal sheep brain (at 58-62 days gestation) is heterogeneous under both control and hypercapnic conditions (especially in the neocortex). Blood vessels of the fetal sheep brain at this early stage of development are clearly responsive to CO2.

Animals↗

PubMed1991

Species-specific transfer of plasma albumin from blood into different cerebrospinal fluid compartments in the fetal sheep.

1. The blood-cerebrospinal fluid (CSF) transfer of endogenous sheep albumin and several exogenous species of albumin has been investigated in different CSF compartments of the immature fetal sheep brain, at an early stage of development (60 days gestation, term is 150 days) when the CSF concentration of total protein is high. 2. There were marked differences in the steady-state CSF/plasma ratios for all species of albumin (including endogenous sheep albumin) between different CSF compartments. Ratios measured in the cisterna magna were significantly higher than those in the dorsal subarachnoid space, which in turn were higher than those in the lateral ventricles. The ratios for endogenous sheep albumin were (%; mean +/- S.E.M.): lateral ventricle (LV), 4.0 +/- 0.03; dorsal subarachnoid (DSA), 6.1 +/- 1.0; cisterna magna (CM), 13.7 +/- 0.8. 3. Three hours after I.V. injection, the CSF/plasma ratios for bovine albumin (LV, 2.0 +/- 0.2; DSA, 2.4 +/- 0.1; CM, 7.2 +/- 0.7%) were significantly lower than the ratio for endogenous sheep albumin in all three compartments. The ratios for human albumin (LV, 0.7 +/- 0.2; DSA, 1.0 +/- 0.2; CM, 3.9 +/- 0.4%) were significantly lower than those for bovine albumin. 4. In all three CSF compartments, the endogenous sheep albumin ratios were higher than would be expected on the basis of transfer by passive mechanisms. Conversely, steady-state CSF/plasma ratios for [3H]sucrose and [14C]inulin were consistent with passive transfer, and there were no differences between the ratios for these markers measured in each of the three CSF regions. 5. Goat albumin and [35S]sheep albumin ratios were not significantly different, 5 h after injection, from the endogenous sheep albumin levels in each of the three CSF compartments. 6. It is concluded that in the 60-day-old fetal sheep, all of the endogenous albumin in CSF is derived from the plasma by a specific transfer mechanism that can distinguish between different species of the same protein. There is also some evidence of a small passive component of blood-CSF albumin transfer. 7. Immunocytochemical evidence suggests that the route of transfer from blood to CSF is transcellular, through the choroid plexus epithelial cells. 8. Regional variations in albumin ratios are probably due to differences in specific transfer into each CSF compartment. This is reflected in a differential immunocytochemical staining for albumin in choroid plexus epithelial cells from different regions of the brain. 9. The results are discussed in terms of differences in albumin amino acid sequences, structural homologies, and transfer by a specific transcellular mechanism.

Albumins↗

PubMed1989

Competition for survival between motor units in mouse skeletal muscle.

The soleus nerve on one side of neonatal mice was crushed and the soleus muscle on the same side was surgically reduced in size. Some animals also had their lumbar spinal nerve 5 (L5) cut and misdirected in the same operation. Three months later, the number of L5 and L6 soleus motor units in the operated muscles was counted electrophysiologically and the number of muscle fibers was counted histologically. The number of L6 motor units in reduced size muscles without L5 innervation was significantly greater than it was in muscles where both L5 and L6 motor units were present. This result supports the concept that motor neuron survival during development is dependent upon the number of muscle fibers available for innervation and the number of motor neurons competing to innervate them.

Action Potentials↗

PubMed1987

End-plate growth exceeds nerve terminal growth in juvenile mice.

An electron microscopic investigation of neuromuscular synapses of the tensor fasciae latae muscle in juvenile mice was carried out to determine the relationship between the presynaptic (nerve terminal) and postsynaptic (end-plate plaque) elements during the major phase of postnatal growth. In the first month of life growth of the synapse was accompanied by a decrease in the size of pre- and postsynaptic elements in cross section. A decrease in the fraction of the width of end-plate plaque opposed by nerve terminal was also observed to age 2 months, and in older animal some end-plate plaques were completely unopposed by nerve terminal. This implies that end plates grow at a faster rate than nerve terminals and suggests that the availability of uninnervated, differentiated end plate permits or promotes nerve terminal growth.

Aging↗

PubMed1984

Muscle size and motor unit survival in mice.

The soleus muscles in neonatal and adult mice were surgically reduced in size on one side of the animal. The experimental and control muscles were excised 6-48 weeks later and the number of motor units in each muscle was estimated by stimulating the muscle nerve and counting step increments in the electromyogram recorded in vitro. Multiple innervation in individual muscle fibres was then assessed by intracellular recording and by visualization of end-plates in the light microscope with cholinesterase stain. Muscle fibres were counted in cross-sections of each muscle in the light microscope. Surgical reductions in the size of the muscle during the first 3 weeks of life produced correlated reductions in the number of motor units in the muscle. This could not be attributed to masking of motor units by multiple innervation, which was always less than 10% in these muscles. The loss of motor units was greatest following reduction in muscle size in newborn mice, whereas in 6-week-old mice there was no significant loss of motor units following the operation. Thus, survival of neonatal motor units shows an age-related dependence on the number of muscle fibres available for innervation. In control muscles there was a highly significant correlation between motor unit and muscle fibre numbers, which is consistent with the hypothesis that motor neurone survival during the embryonic period of cell death is dependent upon the number of muscle fibres available for innervation.

Age Factors↗