Milan Aksić

Volumetric Analysis of Amygdala, Hippocampus, and Prefrontal Cortex in Therapy-Naive PTSD Participants

Objective. In our study we have hypothesized that volume changes of amygdala, hippocampus, and prefrontal cortex are more pronounced in male posttraumatic stress disorder participants. Material and Methods. We have conducted a study of 79 male participants who underwent MRI brain scanning. PTSD diagnosis was confirmed in 49 participants. After MRI was taken all scans were software based volume computed and statistically processed. Results. We found that left amygdala is the most significant parameter for distinction between PTSD participants and participants without PTSD. There were no significant differences in volumes of hippocampi and prefrontal cortices. Roc curve method outlined left amygdala AUC = 0.898 (95% CI = 0.830–0.967) and right amygdala AUC = 0.882 (95% CI = 0.810–0.954) in the group of PTSD participants which makes both variables highly statistically significant. Conclusion. The present investigation revealed significant volume decrease of left amygdala in PTSD patients. Concerning important functions of the amygdala and her neuroanatomical connections with other brain structures, we need to increase number of participants to clarify the correlation between impared amygdala and possible other different brain structures in participants with PTSD.

Clinical significance of blood supply to the internal capsule and basal ganglia

Although the general vascular supply of the basal ganglia and internal capsule is well known, precise data are lacking regarding the variations of the vascular territories in the two regions. Twelve hemispheres were studied following an injection of coloured ink into the main cerebral arteries, namely the anterior cerebral (ACA), middle cerebral (MCA), anterior choroidal (AChA) and posterior cerebral artery (PCA). Serial sections of the injected hemispheres were taken in the axial or coronal plane. In 75% of the hemispheres, ACA perforators were seen to supply the inferomedial part of the head of the caudate nucleus and the anterior limb of the internal capsule, as well as the anterior and inferior portions of the putamen and globus pallidus. The MCA vessels perfused the superolateral part of the head and body of the caudate nucleus, the superior part of the entire internal capsule, most of the putamen and part of the globus pallidus. The AChA perforators perfused the medial segment of the globus pallidus, the inferior part of the posterior limb, the retrolenticular and sublenticular portions of the internal capsule, and occasionally its genu. The same segment of the globus pallidus and the inferior part of the genu of the internal capsule were most likely supplied by the perforators of the internal carotid artery. A predominance of ACA territory was noticed in one specimen (8.33%) and a predominance of MCA territory in two specimens (16.67%). The obtained anatomical data may help radiologic determination of perforators involved in ischemic events, as well as a better understanding of the neurological deficits in the same events.

Common features of the cerebral perforating arteries and their clinical significance

Dear Editor, I would like to thank Matthieu Delion and his colleagues for their compliments regarding our article [1]. At the same time, I am sorry for having not cited their valuable paper [2] on the insular branches of the middle cerebral artery. In general, there are some discrepancies in the terminology and definition of the insular and perforating branches. As we mentioned in our article, there are three main types of the branches of the cerebral arteries: the leptomeningeal, perforating and choroidal [3]. The superficial leptomeningeal vessels give rise to the penetrating branches, i.e. the cortical, subcortical and medullary twigs; the latter of which supply most of the white matter of the cerebral hemispheres, i.e. the centrum semiovale and the corona radiata [4]. On the other hand, the deep perforating vessels mainly originate from the basal cerebral arteries and supply the central hemispheric region, including the basal ganglia and the internal capsule. Accordingly, the mentioned long insular arteries, which arise from the M2 and M3 segments of the MCA, have nothing to do with the perforating vessels of the MCA from both the morphological aspect and the region of supply. These long insular vessels simply belong to the penetrating (medullary) twigs, which were not the subject of our article. As regards the short and medium-sized insular vessels, some of them can be classified as the Batypical^ perforators. However, we presented only the typical perforating arteries, i.e. those with certain common features, as was clearly described in our paper. For that reason, we did not mention the atypical perforators, such as those to the claustrum, the cerebellar roof nuclei and the hypothalamus. In any case, I am grateful to Delion and co-workers for their comment on our article, and for presenting the findings of their research.

Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD) produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach) release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE) activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS) cortex. Wistar rats were separated from their mothers on the postnatal day (P) 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition.

Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase

Maternal deprivation (MD) causes perinatal stress, with subsequent behavioral changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of the major generators of reactive oxygen species, known to play a role in stress response in different tissues. The aim of this study was to elucidate the long-term effects of MD on the expression of NADPH oxidase subunits (gp91phox, p22phox, p67phox, p47phox, and p40phox). Activities of cytochrome C oxidase and respiratory chain Complex I, as well as the oxidative stress parameters using appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats were exposed to a 24 h maternal deprivation and sacrificed at young adult age. The structures affected by perinatal stress, cortex, hippocampus, thalamus, and caudate nuclei were investigated. The most prominent findings were increased expressions of gp91phox in the cortex and hippocampus, increased expression of p22phox and p40phox, and decreased expression of gp91phox, p22phox, and p47phox in the caudate nuclei. Complex I activity was increased in all structures except cortex. Content of reduced glutathione was decreased in all sections while region-specific changes of other oxidative stress parameters were found. Our results indicate the presence of long-term redox alterations in MD rats.

Thermomineral water promotes axonal sprouting but does not reduce glial scar formation in a mouse model of spinal cord injury

Thermomineral water from the Atomic Spa Gornja Trepča has been used for a century in the treatment of neurologic disease. The thermomineral water contains microelements, including lithium and magnesium, which show neural regeneration-promoting effects after central nervous system injury. In this study, we investigated the effects of oral intake of thermomineral water from the Atomic Spa Gornja Trepča on nerve regeneration in a 3-month-old mouse model of spinal cord injury. The mice receiving oral intake of thermomineral water showed better locomotor recovery than those without administration of thermomineral water at 8 and 12 weeks after lower thoracic spinal cord compression. At 12 weeks after injury, sprouting of catecholaminergic axons was better in mice that drank thermomineral water than in those without administration of thermomineral water, but there was no difference in glial reaction to injury between mice with and without administration of thermomineral water. These findings suggest that thermomineral water can promote the nerve regeneration but cannot reduce glial scar formation in a mouse model of spinal cord injury.

Effects of Tetra hydro cannabinol to the dendritc tree and synapses of the accumbens nucleus of Wistar rats.

Cannabis is one of the most widely used intoxicants; almost half of all 18 year olds in the USA and in most European countries admit to having tried it at least once, and ~10% of that age group are regular users. Δ9-Tetrahydrocannabinol (THC), the principal psychoactive ingredient in marijuana, produces euphoria and relaxation and impairs motor coordination, time sense, and short term memory. In the hippocampus, CBs inhibit GABA release from a subset of interneurons and inhibit glutamate release from principal neurons. Cannabinoids are reported to produce both rapid and long-term changes in synaptic transmission. Our study was carried out on ten male rats out of which brains of six of them were used as the representative sample for electron microscope analysis, while 4 were used for light microspcopy performed by Golgi method. Three were exposed to THC and 3 were controls. Axodendric synapses in the core and shell of the accumbens nucleus (AN) were studied under electron microscope. The results have shown widening of the synaptic cleft in the shell of AN. This result is a leading point to our further investigations which are going to involve a behavioral component, and different aspects of morphological studies. [Projekat Ministarstva nauke Republike Srbije, br. III 41020]