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Corticotrophs produce a hormone that stimulates the adrenal gland cortex to secrete glucocorticoids, which in turn have effects on carbohydrate and protein metabolism. Quantification, morphological characteristics, and distribution of corticotrophs in the anterior pituitary and changes in the number and shape of the cells during aging have been examined using immunohistochemical and morphometric methods. The material consisted of 14 anterior pituitaries taken from cadavers at routine autopsy. The tissue was processed by standard histological procedure and the obtained slices were stained by the monoclonal anti-ACTH antibody for corticotrophs identification. Digital images of stained histological sections were analyzed using the morphometric method with the Image J system. The volume density of ACTH positive cells was determined. The cases were classified into three age groups. One-way ANOVA showed that the volume density of the corticotrophs was significantly higher in the second and third group in relation to the first group. The difference in the volume densities of the corticotrophs between the genders was not significant. Morphometric and statistical analyses demonstrated a significant positive correlation between the corticotrophs volume densities and the age of the evaluated cases. Linear regression showed that age significantly predicts corticotrophs volume density. Corticotrophs significantly increase during the life span.

The aim of this research was to quantify the changes in the morphology and density of the anterior pituitary folliculostellate (FS) and luteinizing hormone (LH) cells. Material was tissue of the pituitary gland of the 14 male cadavers. Tissue slices were immunohistochemically stained with monoclonal anti-LH antibody and polyclonal anti-S100 antibody for the detection of LH and FS cells, respectively. Digital images of the stained slices were afterwards morphometrically analyzed by ImageJ. Results of the morphometric analysis showed significant increase of the FS cells volume density in cases older than 70 years. Volume density of the LH cells did not significantly change, whereas their area significantly increased with age. Nucleocytoplasmic ratio of the LH cells gradually decreased and became significant after the age of 70. Finally, volume density of the FS cell significantly correlated with LH cells area and nucleocytoplasmic ratio. From all above cited, we concluded that in men, density and size of the FS cells increase with age. Long-term hypertrophy of the LH cells results in their functional decline after the age of 70. Strong correlation between FS cells and LH cells morphometric parameters might point to age-related interaction between these two cell groups. This article is published in Tissue & Cell (2017), 49(1): 78-85. http://ibiss-r.rcub.bg.ac.rs/123456789/2684

Introduction The aim of our research was to quantify the synaptic density in the parahippocampal region of the brain with densitometric measurements of synaptophysin immunoreactivity in cases of different ages. Methods The study was performed on post mortem obtained right parahippocampal region (PR) samples of 14 cadavers (10 males, 4 females) whose ages ranged from 35 to 80 years. The samples were classified into three age groups (I: 30–49; II: 50–69; III: 70 and older). The tissue was immunohistochemically processed and stained with an anti-human synaptophysin antibody. The densitometric analysis included measurement of the mean and median optical density (OD) of the PR gray and white matter (WM) digital images. This was performed with ImageJ. Results The histological analysis showed that the neuropil of the PR's layers showed two types of synaptophysin positive reactions. The first type was characterized by the presence of a granular pattern of synaptophysin immunoreactivity, and this was less intense in the second type. The synaptophysin immunopositivity of the PR gray matter neuropil decreased with age, especially in its superficial layers. The results of the densitometric analysis confirmed the significant decrease of the gray matter mean and median OD during aging. A One Way ANOVA showed that only the mean and median optical densities of the third age group were significantly lower than the values for the first age group. Discussion The synaptic density decreases with age in the PR, but this decrease is significant only in cases older than 70 years.

Some evidence has suggested that, with age, the hypothalamic–pituitary–adrenal (HPA) axis becomes less resilient, leading to higher glucocorticoids nocturnal levels and a flattening of the circadian profiles. Such age-related changes in the activity of the HPA axis has overexposed the brain and peripheral organs to the effects of the glucocorticoids, increasing the morbidity and mortality rates of the elderly. Debate among scientists regarding the contributions of HPA axis age-related changes of impaired feedback regulation vs. direct overactivation persists. Supporters of impaired feedback regulation assumed that this effect might be the consequence of the hippocampal age-related neuronal loss and the reduction of the number of mineralocorticoid and glucocorticoid receptors. On the other hand, healthy elderly individuals are characterized by an increase of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, and the development of a chronic low-grade inflammatory state, known as inflammaging. Cytokines central to inflammaging send signals to the brain, activate HPA axis, and, by increased cortisol secretion, down-regulate inflammaging in a process known as anti-inflammaging. Even as these cytokines act at the level of the hypothalamic paraventricular nucleus, they are hampered by the intact blood–brain barrier. Further, the corticotropes in the anterior pituitary do not express cytokine receptors, and the density of folliculo-stellate cells generally increases with age. Therefore, we assumed that folliculo-stellate cells were the target structures through which the elevated levels of cytokines, as a part of the inflammaging phenomenon, would cause the overactivation of the HPA axis in healthy elderly individuals. Folliculo-stellate cells are non-endocrine cells that were originally considered to act as supporting cells for the endocrine cells. Despite the fact that FS cells do not produce any of the established hormones of the anterior pituitary, they secrete paracrine agents that act locally to modulate pituitary responses to hypothalamic and peripheral signals. There is evidence of cytokines characteristically involved in inflammaging. For example, IL-1 and TNF-α are thought to stimulate folliculo-stellate cells to release various paracrine agents, including IL-6, IL-11, leukemia inhibitory factor, and macrophage migration inhibitory factor. Through different mechanisms, these agents induce ACTH release by corticotropes. Therefore, it can be concluded that folliculo-stellate cells may act as potent mediators of the age-related HPA axis hyperactivity induced by cytokines characteristic of the inflammaging phenomenon in healthy elderly individuals.

Summary The aim of our study was to analyze the changes of connective tissue sheaths of epi-, peri- and endoneurium of sural nerve during aging. The study was conducted on sural nerve samples of 10 cases aged 9-80 years. The specimens were embedded in paraffin using standard procedures, after which 5-μm-thick cross-sections of nerve trunks were made and stained using Masson’s trichrome staining. After morphological analysis of fascicular structure and connective sheaths of the nerve, morphometric analysis was conducted using the software for digital image analysis “ImageJ”. Each investigated case was analyzed for total neural, epineurial and fascicular cross-section area, mean values of perineurial index, volume density of myelinated axons and of endoneurial content. To test the difference in mean values for statistical significance we used the Student’s T-test for small independent sample. The number of fascicles was 5-13, while the majority of the nerves had less than 10 fascicles. Fascicular structure, which included the number of fascicles and epifascicular/fascicular area ratio, did not show significant changes during aging. Perineurial thickness /fascicle size ratio statistically significantly increased in the older investigated group (p As results of applied investigation methods we found thickening of perineurial sheath of sural nerve during aging, as well as endoneurial fibrosis. Future investigations of age-related changes should focus on analysis of the components of extracellular matrix within perineurium and endoneurium.

The aim of this research was to quantify the number of corpora amylacea and lipofuscin-bearing neurons in the parahippocampal region of the brain. Right parahippocampal gyrus specimens of 30 cadavers were used as material for histological and morphometric analyses. A combined Alcian Blue and Periodic Acid-Schiff technique was used for identification and quantification of corpora amylacea and lipofuscin-bearing neurons. Immunohistochemistry was performed using S100 polyclonal, neuron-specific enolase and glial fibrillary acidic protein monoclonal antibodies for differentiation of corpora amylacea and other spherical inclusions of the aging brain. Cluster analysis of obtained data showed the presence of three age groups (median age: I = 41.5, II = 68, III = 71.5). The second group was characterized by a significantly higher numerical density of subcortical corpora amylacea and number of lipofuscin-bearing neurons than other two groups. Values of the latter cited parameters in the third group were insignificantly higher than the first younger group. Linear regression showed that number of parahippocampal lipofuscin-bearing neurons significantly predicts numerical density of subcortical corpora amylacea. The above results suggest that more numerous parahippocampal region corpora amylacea and lipofuscin-bearing neurons in some older cases might represent signs of its’ neurons quantitatively-altered metabolism.

The continuation of the cranial branch of the primitive internal carotid artery is called the primitive olfactory artery (POℓA). It takes this name according to the fact that it is mainly concerned with supplying the developing nasal region. We reported two new cases of the persistent POℓA (PPOℓA) in Serbian population after retrospective analysis of digital images of 200 fetal and 269 adult cases. This PPOℓA originated from the precommunicating part (A1) of the right anterior cerebral artery, coursed along the olfactory tract, and turned on the medial cerebral hemisphere in both male adults. Some vascular variations (fenestration of the A1 and the median artery of the corpus callosum) were associated with this persistent vessel. According to the fact that we did not find aneurysm in our previous and two recent cases, we are of the opinion that PPOℓA is usually asymptomatic in Serbian population.

Intracranial arterial dolichoectasia is a condition in which arteries demonstrate an increase in length and diameter, with the vertebrobasilar system being the most commonly affected segment. Because the criteria for and degree of vertebrobasilar dolichoectasia are usually established on three-dimensional time-of-flight MR angiography, we presented the results of an anatomic study of vertebrobasilar dolichoectasia cadaveric specimens.Examination was carried out on the brains of human adult cadavers, routinely dissected at the Institute of Forensic Medicine. Measurement of the outer diameter and length of vertebral and/or basilar arteries was performed using the ImageJ processing program.There were 14 cases (14/216) of vertebral and/or basilar (dolicho)ectasia. Their classification into special (sub)types is made according to the basilar and/or vertebral diameter. The basilar length ranged from 32.91-59.37 mm, and the basilar outer diameter ranged from 3.51-8.92 mm in relation to the corresponding point of its measurement. The outer diameter of the vertebral arteries ranged from 0.67-5.91 mm. The Games-Howell post hoc test additionally showed that a basilar outer diameter of grade III and IV was significantly larger than in grade II (p 0.05).We noted a predisposition of males older than 40 years to arterial dolichoectasia in the vertebrobasilar system, independently from population group, as well as its asymptomatic appearance, independently from the presence of atherosclerotic plaques.

Pectoral major flap is one of most frequently used flaps in head and neck reconstruction. The wide attractiveness of this flap is based on secure vascular stalk made from pectoral branch of thoracoacromial artery. The aim of study was to analyze the variations in vascular supply of pectoral major muscle. The investigation was performed on 30 fetuses from 20 to 36 gestation week both gender. For determining vascular network the samples injected with barium sulphate were subjected to Spalteholtz technique, and on 30 fresh cadavers where and we performed injection of Metilen blue 1% in pectoral branch of thoracoacromial artery. In 87% we found one pectoral branch and in 13 % two branches for pectoral muscle were found. Before entering the muscle, pectoral branch is dividing in two terminal branches (67%). In all cases lateral part of pectoral muscle is supplied by branch of lateral thoracic artery. The average area of dyed skin was 13 x 20 cm in region between III and VI rib and from parasternal line to anterior axillar line. The average distance of most distal part of dyed skin to midclavicular point was 24 cm. The pectoral branch of thoracoactomial artery obtains main blood supply for pectoral major muscle mass and despite of anatomical variations can be defined as main pedicle for musculocutaneous flap. Dyed skin confirms that pectoral major flap has defined skin territory sufficient for reconstructions in head and neck area.

The sural nerve is the most frequently used sensory nerve in nerve transplantation. It can be transplanted alone or together with the other elements of the neurovascular stalk within the superficial sural flap. The aim of this study was to define the morphologic types of the sural nerve complex, as well as to describe their specific characteristics. Microdissection was performed on 100 human fetuses (200 calves) after 10% formalin fixation. Five morphologic types of sural nerve complex with different incidence were defined. Two morphologic types dominated: type I (58.5%) in which the sural nerve was formed by merging of a fibular communicating branch and the medial sural cutaneous nerve, and type III (26%) in which the medial sural cutaneous nerve took over the function of the sural nerve. Other morphologic variations were less common.

The posterior cerebral artery (PCA), as a paired terminal branch of the basilar artery, runs through four segments (P1 to P4) to the inferior and medial surfaces of the occipital and a part of the temporal lobes. There are many PCA variants in its course. The literature data indicated that a fenestration of the PCA was very rare and that its clinical significance is unknown. The purpose of this investigation was to present the frequency, location, and some morphological features of PCA fenestration in the prenatal and postnatal period. Using brain bases of 468 (200 fetal and 268 adult) cadavers, we applied macroscopic and microscopic investigation. We found four (0.85 %) cases of PCA fenestrations—two at the left and right P1 segment of fetuses, respectively, then one adult at the left P2 segment, as well as one adult at one right PCA of the two existing arteries. There were associated multiple vascular abnormalities in one adult case. We did not find any case of PCA aneurysm originating from fenestration, as well as from PCA without fenestration. The frequency, segment, and side location, as well as the size and shape of PCA fenestrations in specimens of our population did not significantly differ from the same in other populations. PCA fenestrations in our adult specimens were not the bases of aneurysms.

Unusual widening of the posterior communicating artery (PCoA) at its beginning from the cerebral portion of the internal carotid artery (ICA) was described as its infundibular dilatation (ID). A possibility of ID rupture or progression to aneurysm was the reason for an investigation of its frequency and morphologic features in specimens of the Serbian population. Cerebral arteries on the brain base of 267 adult cadavers of both genders and varying age and causes of death were dissected. The images of the PCoA in 190 fetuses were also reviewed. ID of the PCoA was defined as a funnel shaped beginning of different width from ICA, wherein PCoA continues from ID apex to the posterior cerebral artery. There were no cases of ID in fetuses. ID and aneurysms of the PCoA were found in 6/267 or 2.2% and 3/267 or 1.12% of adults, respectively. Unilaterally, they existed on the left side and, frequently, in male cases aging 70 years and older, that had died without cerebral cause. Bilaterally, ID was found in 2/6 cases. There was only one case of ID and aneurysm of the PCoA, but from the ID. We are of the opinion that ID of the PCoA only develops postnatally and probably is due to the influence of hemodynamic factors or hypertension.

One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P<0.05) and endoneurial connective tissue percentage (P<0.01). The diabetic group showed significantly higher epineurial area (P<0.01), as well as percentage of endoneurial connective tissue (P<0.01), in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves.

In the literature, there are descriptions of morphological types of the cerebral arterial circle (CAC) of different human populations around the world, but not the Serbian population. This additionally inspired the authors to present the results of previous and current researches of CAC’s configuration in the prenatal, as well as in the postnatal period. The study was performed on CACs of 190 human fetuses and 143 adult cadavers. The caliber and configuration of fetal vessels were examined under the operating microscope, while the same of adults were studied using the ImageJ. Statistical analysis of CACs vessels’ calibers was performed. Classification into one of CAC morphological types was based on the presence of hypoplasia of corresponding vessel(s). There was not only significant difference of the three communicating arteries calibers before and beyond the 16th week of gestation. Calibers of the right pre-communicating part of the posterior cerebral artery and right cerebral part of the internal carotid artery were significantly higher in male than in female adults. There were 13 morphological types of CACs from the prenatal to the postnatal period. Most frequent CAC types were the type I (normal CAC) prenatally and type IV (unilateral hypoplasia of the posterior communicating artery) in the postnatal period. There were not relationships between the cerebral cause of death and a presence of aneurysm. Results of this study will be the basis for future investigation of CACs according to the same or different ages and causes of disease and/or death.

Folliculostellate cells represent non-endocrine cells of the anterior pituitary which influence the function of the endocrine cells via paracrine action. Though there is a lack of literature data on their presence during human aging, the aim of this research was to perform the quantification of anterior pituitary folliculostellate cells by the application of immunohistochemical and morphometric methods. The material for the study consisted of 15 anterior pituitaries taken from cadavers at routine autopsy. Their tissue was processed by standard histological procedure and the obtained histological slices were stained by S100 polyclonal antibody. Digital images of stained histological sections were analyzed by morphometric method with ImageJ system. The volume density of S100 positive cells was measured for each case. Results of morphometric and statistical analysis showed a significantly positive correlation between folliculostellate cell volume density and the age of the evaluated cases. Linear regression additionally showed that the age significantly predicts folliculostellate cells volume density in our sample. Further, all cases were classified into three age groups and One Way ANOVA showed that the volume density of folliculostellate cells was significantly higher only in the third age group in relation to the first and the second group, respectively. Volume densities of the first and the second age groups were not significantly different. So, the results of our study pointed to the conclusion that folliculostellate cells presence generally increases with age, but this increase is significant only in the oldest cases and might represent the modality of successful anterior pituitary aging.

The main cerebral distribution center of 15-20% blood flow from the cardiac output is the cerebral arterial circle or circle of Willis, a nonagon of collateral vessels on the human brain base. At about 4 mm stage of the embryo, the primitive internal carotid arteries, which develop as cranial extensions of the paired dorsal aorta, are formed. Paired longitudinal neural arteries appear along the hindbrain and coalesce to form the basilar trunk at the 7to 12-mm stage. The caudal division of the primitive internal carotid artery anastomoses with ipsilateral neural artery and becomes the posterior communicating artery. At the 40-mm stage the posterior cerebral arteries are as extensions of the posterior communicating arteries. The vertebrobasilar system develops and thus participates in the supply of the posterior cerebral artery through the segment between the basilar artery and the post-communicating part of the posterior cerebral artery. In that phase, the component vessels of the circle of Willis all have the same caliber (Silver & Wilkins, 1991). The posterior cerebral artery originates from the basilar bifurcation within the interpeduncular cistern. From its origin the artery curves superior to the corresponding oculomotor nerve in relation to the antero-medial portion of the cerebral peduncle and joins ipsilateral posterior communicating artery (Yasargil, 1984). The posterior communicating artery takes origin from the infero-lateral wall of the cerebral part of the internal carotid artery. It is encased in a sleeve of arachnoid along the course from the carotid cistern to the piercing of the interpeduncular cistern and junction with posterior cerebral artery (Yasargil, 1984). Topographically, the circle of Willis is divided on anterior and posterior parts. The anterior part composes five vascular components – bilateral cerebral parts of internal carotid arteries (communicating and choroid subparts) and the pre-communicating part of anterior cerebral arteries interconnected by the anterior communicating artery; the posterior part composes

Carotid–vertebrobasilar anastomoses—the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries—serve as transitory channels between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery, when the human embryo reaches about 4-mm length. Normal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the trigeminal artery are described according to personal and literature data. Many arteries of similar origin and course are also noted in the differential diagnosis of the trigeminal artery. The persistent primitive trigeminal artery, as the most commonly carotid–vertebrobasilar anastomosis, has a reported incidence of 0.03–2.2% in the literature. There is female sex predilection, and it may be discovered in patients of any age, on either side, and in association with many vascular variants. Although the significance of persistent primitive trigeminal artery regarding the development of an aneurysm or association with another pathological condition may not be clear, its (ab)normal morphology is the inspiration for anatomists, especially for neurosurgeons, before planning diagnostic and therapeutic procedures.