Slađana Ugrenović

Trigeminal artery: a review of normal and pathological features

ObjectsCarotid–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.Material and methodsNormal 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.ConclusionsThe 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.

Morphology of the cerebral arterial circle in the prenatal and postnatal period of Serbian population

BackgroundIn 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.MethodThe 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).ResultsThere 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.ConclusionResults 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.

Morphometric Analysis of Connective Tissue Sheaths of Sural Nerve in Diabetic and Nondiabetic Patients

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.

Types and Subtypes of the Posterior Part of the Cerebral arterial Circle in Human Adult Cadavers

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

Analysis of Fascicular Structure and Connective Tissue Sheaths in Sural Nerve during Aging

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<0.05). Myelinated fibres were of smaller diameter, with more irregular form and markedly less frequent in older cases. Quantitative analysis showed statistically significant decrease in volume density of myelinated fibres in the older group. 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.

Persistent Primitive Olfactory Artery in Serbian Population

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.

Infundibular dilatation of the posterior communicating artery in a defined population

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.

Morphometric analysis of the human anterior pituitary's folliculostellate cells during the aging process

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.

Folliculo-stellate cells – Potential mediators of the inflammaging-induced hyperactivity of the hypothalamic–pituitary–adrenal axis in healthy elderly individuals

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.

Morphometric analysis of the folliculostellate cells and luteinizing hormone gonadotropic cells of the anterior pituitary of the men during the aging process

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.