Mean Neuronal Size Research Articles

Anatomy and neural remodeling of the renal sympathetic nerve in a canine model and patients with hypertension.

The role of renal sympathetic nerve (RSN) in hypertension should be better understood. We aimed to three-dimensionally reconstruct the renal nerves, and explore its anatomical and histochemical characteristics in hypertensive canine model and patients. Renal arteries with surrounding tissue were collected from canines and cadavers with or without hypertension. Serial renal artery hematoxylin-eosin sections were used for three-dimensional reconstruction, and morphological parameters were collected and analyzed. In hypertensive canines, the mean renal nerve number was 26.71 ± 5.68 versus 19.84 ± 5.68 in controls (P = 0.02), and the middle renal nerve volume was 5.31 ± 2.13 versus 2.60 ± 1.00 μl in controls (P = 0.01). Renal tissue norepinephrine concentrations, tyrosine hydroxylase and substance P immunoreactivity in RSN, and growth-associated protein 43 immunoreactivity in renal ganglion were significantly increased in hypertensive canines. In humans, the renal nerve was evenly distributed along the renal artery in a network pattern. The renal ganglion volume was 72.75 ± 33.43 in hypertensive patients versus 37.04 ± 23.95 μl in controls (P = 0.029) and the mean neuronal size in renal ganglion was 1187.3 ± 219.9 μm in patients versus 714.8 ± 142.7 μm in controls (P = 0.002). Tyrosine hydroxylase immunoreactivity in the RSN was 0.153 ± 0.014 in patients versus 0.104 ± 0.019 in controls (P = 0.013). Growth-associated protein 43 immunoreactivity in the renal ganglion was 86 612.8 ± 14 642.0 in patients versus 33 469.8 ± 15 666.8 μm/mm in controls (P < 0.001). Our study suggests that RSN and renal ganglion histological remodeling occurs in individuals with hypertension and the distal segment or branches of renal artery might be a promising therapeutic target for RSN modulation therapy.

Morphometric Characteristics of the Structure of the Central Nucleus of the Amygdaloid Complex in Men and Women

Objectives. To identify interhemisphere asymmetry in the structure of the central nucleus of the amygdaloid complex in men and women. Materials and methods. The morphometric characteristics of neuron structure in the central nucleus of the amygdaloid complex were determined on histological sections of the brain from six men and six women (24 hemispheres) aged 19–55 years with no history of mental or neurological disease while alive. Neuron profile field sizes were determined in the central nucleus of the amygdaloid complex in the left and right hemispheres of the brain. Results and discussion. Mean neuron size in women was somewhat larger in the left hemisphere than the right, while mean neuron size in men was greater on the right. Neither men nor women showed any statistically significant interhemisphere morphometric differences. Furthermore, neuron profile field size in the central nucleus of the amygdaloid complex in women was statistically significantly larger than in men in both hemispheres. An attempt was made to link these data with the characteristics of emotional perception in men and women.

Remodeling of stellate ganglion neurons after spatially targeted myocardial infarction: Neuropeptide and morphologic changes.

Myocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs). We investigated whether infarct site has any impact on the laterality of morphologic changes or neuropeptide expression in stellate ganglia. Yorkshire pigs underwent left circumflex coronary artery (LCX; n = 6) or right coronary artery (RCA; n = 6) occlusion to create left- and right-sided MI, respectively (control: n = 10). At 5 ± 1 weeks after MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, as well as tyrosine hydroxylase (TH) and neuropeptide Y immunoreactivity. Compared with control, LCX and RCA MIs increased mean neuronal size in the LSG (451 ± 25 vs 650 ± 34 vs 577 ± 55 μm(2), respectively; P = .0012) and RSG (433 ± 22 vs 646 ± 42 vs 530 ± 41 μm(2), respectively; P = .002). TH immunoreactivity was present in the majority of SGNs. Both LCX and RCA MIs were associated with significant decreases in the percentage of TH-negative SGNs, from 2.58% ± 0.2% in controls to 1.26% ± 0.3% and 0.7% ± 0.3% in animals with LCX and RCA MI, respectively, for LSG (P = .001) and from 3.02% ± 0.4% in controls to 1.36% ± 0.3% and 0.68% ± 0.2% in LCX and RCA MI, respectively, for RSG (P = .002). Both TH-negative and TH-positive neurons increased in size after LCX and RCA MI. Neuropeptide Y immunoreactivity was also increased significantly by LCX and RCA MI in both ganglia. Left- and right-sided MIs equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced after MI result in bilateral changes and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation.

Neural systemic impairment from whole-body vibration.

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments.

Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias

5.1 Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias O.A. Ajijola, J.J. Wisco, H.W. Lambert, E.M. Stark, A. Mahajan, M.C. FIshbein, K. Shivkumar (University of California, Los Angeles, CA, USA), (West Virginia University, Morgantown, WV, USA) Background: Intra-myocardial nerve sprouting after myocardial infarction is associated with ventricular arrhythmias (VAs). Whether human stellate ganglia remodel in association with cardiac pathology was unknown. The purpose of our study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. Methods and Results: Left stellate ganglia (LSG) were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias, and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed extensively. We classified ganglia from normal; scarred; and non-ischemic cardiomyopathic hearts without scar as NL (n = 3); SCAR (n = 24); and NICM (n = 7), respectively. Within LSG, we measured neuronal size, density, fibrosis, synaptic density and nerve sprouting. Nerve density and sprouting were also quantified in obtained cadaveric hearts. Mean neuronal size in NL, SCAR, and NICM groups were; 320 ± 4 μm, 372 ± 10 μm, and 435± 10 μm (p= 0.002). No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in SCAR and NICM ganglia were 57.8 ± 11.2um/mm (p= 0.039) and 44.5 ± 7.9um/mm (p= 0.084) respectively, compared to the NL, 17.8 ± 7um/mm (overall p = 0.162). There were no significant differences in LSG nerve sprouting ormyocardial nerve density between the groups. In a porcinemodel of chronic infarcts, neurochemical changes were also observed in addition to increased neuronal size. Conclusions: Neuronal hypertrophy within LSG is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial nerve sprouting and nerve density were not significantly different. A porcine model recapitulates these findings, and demonstrates neurochemical rmodeling. These changes may be related to increased cardiac sympathetic signaling and VAs. Further studies are needed to determine the electrophysiologic consequences of extra-cardiac neuronal remodeling in humans. doi:10.1016/j.autneu.2013.05.030

Extracardiac Neural Remodeling in Humans With Cardiomyopathy

Intramyocardial nerve sprouting after myocardial infarction is associated with ventricular arrhythmias. Whether human stellate ganglia remodel in association with cardiac pathology is unknown. The purpose of this study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. Left stellate ganglia were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed. We classified ganglia from normal, scarred, and nonischemic cardiomyopathic hearts without scar as NL (n=3), SCAR (n=24), and NICM (n=7), respectively. Within left stellate ganglia, neuronal size, density, fibrosis, synaptic density, and nerve sprouting were determined. Nerve density and sprouting were also quantified in cadaveric hearts. Mean neuronal size in normal, scarred, and nonischemic cardiomyopathic hearts without scar groups were 320 ± 4 μm(2), 372 ± 10 μm(2), and 435 ± 10 μm(2) (P=0.002), respectively. No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in ganglia from SCAR and NICM groups were 57.8 ± 11.2 μm(2)/mm(2) (P=0.084) and 44.5 ± 7.9 μm(2)/mm(2) (P=0.039), respectively, compared with the normal group, 17.8 ± 7 μm(2)/mm(2) (overall P=0.162). There were no significant differences in left stellate ganglia nerve sprouting or myocardial nerve density between the groups. Neuronal hypertrophy within left stellate ganglia is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial nerve sprouting and nerve density were not significantly different. These changes may be related to increased cardiac sympathetic signaling and ventricular arrhythmias. Further studies are needed to determine the electrophysiological consequences of extracardiac neuronal remodeling in humans.

Zonisamide Attenuates MPTP Neurotoxicity in Marmosets

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces parkinsonism in humans and animals. The effects of zonisamide on dopamine neurons were studied in MPTP-treated common marmosets (Callithrix jacchus). Groups of animals (n = 3) were treated with MPTP (2.5 mg/kg, every 24 h x 3); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (a known MAO-B inhibitor) (2 mg/kg administered 1 h before each MPTP dose); and saline controls. An immunohistochemical study of the substantia nigra was performed 14 days after MPTP treatment in each group. MPTP reduced the mean number of tyrosine hydroxylase (TH)-positive neurons to 10% of the normal control group and mean cell size was significantly (P < 0.001) reduced from 424 to 159 µm². In the group pre-treated with zonisamide, the mean number of TH-positive neurons was reduced to 26% of that in the normal control group and the mean neuron size was significantly (P < 0.05) increased from 159 to 273 µm² compared with the group treated with MPTP alone. Moreover, in the group pre-treated with selegiline, the mean number of TH-positive neurons was 47% of that in the normal control group and the mean neuron size was increased significantly (P < 0.01) from 159 to 319 µm² compared to the group treated with MPTP alone. This observation suggests that zonisamide reduces MPTP toxicity.

Quantification of the neurodegenerative impact on the visual system following sudden retrobulbar expanding lesions – an experimental model

Introduction: Afferent disorders of the visual system are a potential consequence following orbital trauma. The aim of this study was to investigate the tolerance of neurons in the retinal ganglion cell layer to acute expanding retrobulbar lesions. Material and methods: In 42 male albino rats, intraorbital haemorrhage was simulated by transconjunctival insertion of a retrobulbar micro-balloon (filling volume 0.2–0.5 ml, duration of lesion 60 or 90 min). Neurodegeneration in the retinal ganglion cell layer was investigated by measuring the mean total neuron number and the mean neuron size. Results: Increased retrobulbar volumes of 0.3 ml for 60 min led to a decrease in a number of neurons by 14.5% and in size of the neurons by 1.7%. Prolongation of the trauma to 90 min resulted in a decrease in number of neurons by 48.3% and in reduction of size of neurons by 22.1%. In contrast, a retrobulbar filling volume of 0.5 ml for 60 min resulted in a decrease in number of neurons by 11.4% and in size of neurons by 6.7%. Conclusion: The duration of a retrobulbar lesion leading to subsequent retinal ischaemia seems to be more important for neuron survival than the exerted pressure (once it is greater than a critical point for producing retinal ischaemia). The results strengthen the need for emergency treatment in cases of retrobulbar haemorrhage. Copyright 2002 European Association for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.

The interstitial nuclei of the human anterior hypothalamus: an investigation of sexual variation in volume and cell size, number and density

The four interstitial nuclei of the anterior hypothalamus (INAH) have been considered as candidate human nuclei for homology with the much studied sexually dimorphic nucleus of the preoptic area of the rat. Assessment of the INAH for sexual dimorphism has produced discrepant results. This study reports the first systematic examination of all four INAH in the human for sexual variation in volume, neuronal number and neuronal size. Serial Nissl-stained coronal sections through the medial preoptic area and anterior hypothalamus were examined from 18 males and 20 females who died between the ages of 17 and 65 without evidence of hypothalamic pathology or infection with the human immunodeficiency virus. A computer-assisted image-analysis system and commercial stereology software package were employed to assess total volume, neuronal number and mean neuronal size for each INAH. INAH3 occupied a significantly greater volume and contained significantly more neurons in males than in females. No sex differences in volume were detected for any of the other INAH. No sexual variation in neuronal size or packing density was observed in any nucleus. The present data corroborate two previous reports of sexual dimorphism of INAH3 but provide no support for previous reports of sexual variation in other INAH.

Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease.

The cortex of patients with schizophrenia exhibits a deficit in neuropil, but the nature and extent of cellular abnormalities remain unclear. To gain further insight into this abnormality, neuronal and glial somal size were analyzed in postmortem brains from 9 patients with schizophrenia, 10 normal (control) patients, and 7 patients with Huntington disease, the latter representing a known neurodegenerative disorder. A 3-dimensional image analyzer was used to measure the perimeters of 10722 neuronal and 19913 glial profiles in Brodmann areas 9 and 17. Neurons and glia were classified by size and layer to assess specific vulnerabilities with respect to cortical architecture and circuitry. The schizophrenic prefrontal cortex was characterized by a downward shift in neuronal sizes accompanied by 70% to 140% per layer increases in the density of small neurons. In layer III only, a significant reduction in mean neuronal size was associated with a significant decrease in the density of very large neurons in sublayer Illc. Neither neuronal size in occipital area 17 nor glial size in prefrontal or occipital cortexes were reduced. In cortex with Huntington disease, neuronal degeneration was evidenced by concurrence of reduced neuronal size, decreased density of large neurons, and dramatic elevation in density of large glia. Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal cortex is not a prominent feature of the neuropathological changes in schizophrenia, although an ongoing process in Huntington disease. Rather, schizophrenia appears to involve more subtle abnormalities, with the largest corticocortical projection neurons of layer IIIc expressing the greatest somal reduction.

Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein

Neuronal density, neuron size, and the number of neurons under 1 mm 2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm 2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

Influence of fetal brain grafts on axotomized retinal ganglion cells

The neurotrophic activity of fetal brain grafts next to the proximal stump of the transected optic nerve of adult rats was investigated. Axotomy ( n= 25) reduced the original retinal ganglion cell population by 90% and the mean neuron size by one-third within 30 days. No increase in number or size of the surviving neurons could be found in any group receiving an embryonic brain graft (E16; spinal cord: n=16, cerebral cortex: n=16, tectum: n=15, thalamus: n= 17) at the site of optic nerve transection, despite good survival of transplants. Although no positive effect on axotomized retinal ganglion cells could be found after transplantation of embryonic central nervous system structures, the same experimental model of the optic nerve seems to be valuable for further investigations of degeneration of traumatized retinal ganglion cells.

HIV-1-associated cognitive/motor complex: absence of neuronal loss in the cerebral neocortex.

We performed a postmortem morphometric study in six AIDS patients and six controls to determine if a neocortical neuronal loss occurs in HIV-1-associated cognitive/motor complex. Patients were selected during a prospective study including psychometric evaluation and neuroimaging, and none had focal lesions. Two had HIV-1-associated myelopathy with mild cognitive impairment, and four had HIV-1-associated dementia complex. Planimetry did not show any cerebral atrophy. Cortical thickness, mean neuronal size, and mean neuronal densities in Brodmann's areas 4, 9, and 40 were not statistically different in patients and controls. There were no significant changes in neuronal densities of columnar and laminar samples, indicating that there was neither global nor selective neuronal loss. HIV-1-associated cognitive/motor complex is not necessarily related to neocortical neuronal loss, but could be due to subcortical lesions or metabolic dysfunction.

The effects on fetal brain development in the rat of a severely iodine deficient diet derived from an endemic area: observations on the first generation.

Rats were fed on a severely iodine deficient diet (iodine content 4.5 micrograms/100 g) similar to that being consumed by people living in a village with a high rate of endemic cretinism. After a period of 4 months, the thyroid and brain were studied in the adult and their fetuses at 16, 17, 18, 19 and 20 days of gestation, and in postnatal animals at 1, 5, 10, 20, 30 and 60 days of age. By comparison with a control group (diet with iodine content 54.7 micrograms/100 g) the experimental group showed marked goitres, a higher uptake of 125I by the thyroid, reduced serum T4, and reduction in brain weight. The cerebral and cerebellar histological findings showed that the density of brain cells had increased, and the mean neuron size was reduced. Furthermore, disappearance of the cerebellar EGL was delayed. These findings indicate that this animal model is likely to be suitable for the studies of endemic cretinism in man.

Immunohistochemical localization of neuropeptide Y in the guinea pig medulla oblongata. Correlation with VIP and DBH.

The immunohistochemical localization of neuropeptide Y (NPY) was correlated with those of dopamine-beta-hydroxylase (DBH) and vasoactive intestinal polypeptide (VIP) by mapping serial 7 micron paraffin sections at three levels of the guinea pig lower brainstem: a) area postrema, b) dorsal motor nucleus of the vagus, and c) nucleus prepositus of the hypoglossal nerve. Based on differences in transmitter expression, three populations of NPY-immunoreactive (IR) neurons were distinguished: NPY-IR catecholaminergic cells (NPY/CA), NPY-IR VIP-ergic cells (NPY/VIP), and NYP-IR cells which were not reactive to either DBH or VIP. Within these populations, size differences among neurons in characteristic locations allowed differentiation among the following subpopulations: NPY/CA neurons in the lateral reticular nucleus--magnocellular part (mean neuronal size 538 micron2) and parvocellular part (318 micron2)-, in the vagus-solitarius complex (433 micron2), and in the dorsal strip (348 micron2); NPY/VIP neurons in the vagus-solitarius complex (368 micron2) and in the nucleus ovalis (236 micron2). Apart from scattered NPY-IR cell bodies in the regions listed above, NPY-IR cell bodies in the lateral portion of the nucleus solitarius and in the caudal part of the spinal nucleus of the trigeminal nerve did not exhibit IR to either DBH or VIP. NPY-IR neurons in the area postrema occurred too infrequently for co-localization studies. The differential distribution of heterogeneous NPY-IR cell subpopulations may reflect the involvement of NPY in a variety of neuronal functions.

Afferent influences on the development of the brain stem auditory nuclei of the chicken: Otocyst ablation

The effects of embryonic deafferentation on the morphological development of the avian cochlear nuclei, n. angularis (NA) and n. magnocellularis (NM), were investigated. The right otocyst was surgically removed from chick embryos at 55 to 60 hours of incubation and the subsequent development of total volume, neuron number, and neuron cross-sectional area were studied with quantitative methods in animals sacrificed at 2-day intervals between embryonic days 9 and 19 and at 28 days posthatching. The development of NA and NM is severely affected by otocyst ablation. Between embryonic days 9 and 19, a large group of NA neurons in the medioventral portion of the nucleus on the operated side moves to an ectopic ventromedial position, while the remainder of this nucleus stays in its normal dorsolateral position. Beginning about day 13 of incubation, the normal increase in the volume of NA and the size of its neurons becomes progressively retarded and 40% of its neurons are lost. The growth of NM is also retarded after day 11 of incubation and the growth of mean neuron size is retarded after day 15. There is a 30% loss of neurons in NM which begins after embryonic day 11. The results indicate the primary cochlear fibers make a critical contribution to the growth and maintenance of their target neurons. The absence of this facilitative influence following otocyst ablation becomes apparent just at the time synapses would normally be formed between the the primary auditory afferents and the brain stem auditory neurons. The abnormal movement of neurons in nucleus angularis to an ectopic position after otocyst ablation suggests that primary auditory afferents may serve to stabilize the position of their target cells within the developing brain.