Lamina Terminalis Research Articles

Circumventricular Organs: Area Postrema, Median Eminence and Neurohypophysis, Subcommissural Organ, Pineal Gland and Choroid Plexus

There are seven circumventricular organs in the rat brain, which have been given this classification because they are all located in the walls of the lateral, third, or fourth ventricles of the brain. The subfornical organ, the vascular organ of the lamina terminalis (OVLT), the pineal gland, the subcommissural organ, and the median eminence/neurohypophyseal complex are located in different places in the wall of the third ventricle. The area postrema is located in the wall of the fourth ventricle. The choroid plexus can be found in the lumen of the lateral, third, or fourth ventricle.

Abstract 54: The kidney-OVLT axis in renovascular hypertension: Individual and combined effects of afferent renal denervation and OVLT lesion in 2K1C rats.

We have recently reported that afferent renal denervation (ARDN) markedly attenuates the pathogenesis of hypertension in the 2 kidney 1 clip (2K1C) model in the rat. This was associated with a reduction in neurogenic pressor activity (NPA). We have also recently shown that lesion of the organum vasculosum of the lamina terminalis (OVLT), a forebrain circumventricular organ, had nearly identical effects in 2K1C rats as ARDN. Together these findings suggest that a neural pathway from the kidney to the OVLT plays an important role in 2K1C hypertension. Based on these findings we hypothesized that the combined effect of ARDN and lesion of the OVLT (OVLTx) on arterial pressure in 2K1C rats would not be greater than the individual treatments. Male Sprague-Dawley rats were randomly selected to receive either OVLT lesion (x) or sham-OVLTx. One week later, rats were instrumented with telemeters to measure mean arterial pressure (MAP). One week later, renal artery stenosis was created by placing a clip on the left renal artery and then, rats were subjected to ARDN by periaxonal capsaicin or sham treatment of the clipped kidney creating 4 experimental groups: sham+sham (n=6), sham+ARDN (n=6), OVLTx+sham (n=5), OVLTx+ARDN (n=5). MAP was measured daily for 28 days, and at the end of the protocol, NPA was assessed by measuring the peak MAP response to ganglionic blockade. MAP was similar in all 4 groups at the beginning of the study averaging 108±3 mmHg. MAP increased to 180±10 mmHg in the sham+sham group compared to 130±13mmHg in sham+ARDN, 142±18mmHg in OVLTx+sham rats and 158±14mmHg in OVLTx+ARDN rats (p<0.001). NPA in Sham+sham rats was significantly higher (-44 ± 8 mmHg) compared to sham+ARDN (-18 ± 3 mmHg), OVLTx+sham (-21 ± 2 mmHg) and OVLTx+ARDN (-19 ± 4 mmHg) rats (p<0.05). Notably, the combined effects of OVLTx+ARDN on MAP and NPA were not significantly different from either OVLTx (p=1.00 and p=0.819) or ARDN (p=0.113 and p= 0.878) alone. In summary, ARDN and OVLTx attenuated hypertension and NPA similarly in 2K1C-HTN rats but the combination of these treatments did not produce any additional effect on MAP or NPA. These findings are consistent with the hypothesis that afferent renal nerves and the OVLT are linked in a common neural pathway required for the development of hypertension following renal artery stenosis.

Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission.

Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins (Dorland 2020). Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland (Popa & Fielding 1930). The second was discovered a few years ago, and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO) (Yao et al. 2021). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu (McKinley et al. 2003). They line the surface of brain ventricles and bear fenestrated capillaries, thereby lacking blood brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. This has been difficult to establish as the structures lie at the midline and protrude into the ventricular space. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light-sheet microscopy to acquire volumetric images of blood vessels. The results indicate that there is a portal pathway linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the latter arrangement, the AP and the nucleus of the solitary tract share their capillary beds. Taken together, the results reveal that all three sensory circumventricular organs bear specialized capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.

A Cadaveric Feasibility Study of the Biportal Endoscopic Transfrontal Sinus Approach: A Minimally Invasive Approach to the Anterior Cranial Fossa.

The trans-sinus transglabellar and bifrontal approaches offer direct access to the anterior cranial fossa. However, these approaches present potential drawbacks. We propose the biportal endoscopic transfrontal sinus (BETS) approach, adapting endoscopic endonasal approach (EEA) techniques for minimally invasive access to the anterior fossa, reducing tissue manipulation, venous sacrifice, and brain retraction. Six formalin specimens were used. BETS approach involves 2 incisions over the medial aspect of both eyebrows from the supraorbital notch to the medial end of the eyebrow. A unilateral pedicled pericranial flap is harvested. A craniotomy through the anterior table of the frontal sinus (FS) and a separate craniotomy through the posterior table are performed. Two variants of the approach (preservative vs cranialization) are described for opening and reconstruction of the FS based on the desired pathology to access. Bone flap replacement can be performed with titanium plates and filling of the external table defect with bone cement. Like in EEA, this approach provides access for endoscope and multiple working instruments to be used simultaneously. The approach allows wide access to the anterior cranial fossa, subfrontal, and interhemispheric corridors, all the way up to the suprachiasmatic corridor and through the lamina terminalis to the third ventricle. BETS provides direct access to the anterior fossa, minimizing the level of frontal lobe retraction and providing potentially less tissue disruption and improved cosmesis. Cerebrospinal fluid fistula risk remains one of the major concerns as the narrow corridor limits achieving a watertight closure which can be mitigated with a pedicled flap. Mucocele risk is minimized with full cranialization or reconstruction of the FS. The BETS approach is a minimally invasive approach that translates the concepts of EEA to the FS. It allows excellent access to the anterior cranial fossa structures with minimal frontal lobe retraction.

Blood flows from the SCN toward the OVLT within a new brain vascular portal pathway.

The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.

Variation in optic recess angle with optic chiasm position

Background: The position of the optic chiasm relative to surrounding structures is critical in planning surgical interventions for suprasellar lesions. This study explored the relationship between the angle of the optic chiasm and lamina terminalis (OC-LT) and the position of the optic chiasm. Methods: The study comprised 140 individuals who underwent midsagittal and axial MRI-T2 scans. The position of the optic chiasm was classified into three categories: sellar, prefixed, and postfixed. The OC-LT angle was measured in the midsagittal section. Results: The angle between OC-LT varied from 30 to 66 degrees with a mean of 46.6 degrees. The sellar position of the optic chiasm was predominant (85.2%), with smaller angles (30-39 degrees) significantly associated with a sellar chiasm location. Most cases with postfixed optic chiasm fell within a 40-49 degree angle range. Conclusions: The OC-LT angle variability can be linked to the position of the optic chiasm. Predominantly, smaller angles correlated with a sellar position of the optic chiasm, while larger angles were associated with a postfixed optic chiasm. This information is crucial for surgical planning in the suprasellar region.

Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study

Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults. Resting-state fMRI scans were acquired in 13 participants at baseline and during a 30 min hypertonic saline infusion (HSI). We used a seed-based approach to analyze the data, focusing on the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) as regions of interest (ROIs). Blood chemistry and perceived thirst were assessed pre- and post-infusion. As expected, serum sodium increased from pre- to post-infusion in the HSI group. The primary finding of this pilot study was that the functional connectivity between the SFO and a cluster within the OVLT increased from baseline to the late-phase of the HSI. Bidirectional connectivity changes were found with cortical regions, with some regions showing increased connectivity with sodium-sensing regions while others showed decreased connectivity. Furthermore, the functional connectivity between the SFO and the posterior cingulate cortex (a control ROI) did not change from baseline to the late-phase of the HSI. This finding indicates a distinct response within the NaCl sensing network in the human brain specifically related to acute hypernatremia that will need to be replicated in large-scale studies.

WNK1 is a central osmolality sensor for arginine vasopressin release and acts through the OSR1/SPAK kinase cascade

Background: Maintaining internal osmolality constancy and water homeostasis is essential for life. The circumventricular organs (CVOs) of the brain, including the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO), lack a blood-brain barrier. Neurons in OVLT and SFO detect increases in serum osmolality that stimulate the production of vasopressin (AVP) in paraventricular nuclei (PVN) to be released in the posterior pituitary. We have recently reported that WNK1 in sensory neurons in CVOs functions as an osmolality sensor for AVP release (Jin et al., JCI, 2023). WNK1 activates Kv3.1 to increase action potential, traveling down to PVN to increase AVP synthesis for release from the posterior pituitary. Here, we propose that OSR1/SPAK acts as the downstream kinase for WNK1 in regulating AVP release. We further investigated the regulation of vasopressin release by the WNK1-OSR1/SPAK cascade in response to extracellular hyperosmolality. Methods: Cre recombinase-carrying retrograde AAV virus was stereotaxically injected into PVN nuclei from normal mice and SPAK-null mice with a homozygous OSR1-floxed allele (SAPK−/−;OSR1flox/flox). Metabolic cage studies were performed on mice. Urine output, water intake, serum osmolality, serum AVP, and copeptin levels were measured. K+ currents were measured from the OVLT neurons by whole-cell patch clamp. Results: Increased osmolality, either by water restriction or mannitol injection, activated OSR1/SPAK in OVLT, as evident by increased serine-373 phospho-SPAK and serine-325 phospho-OSR. Like the WNK1 deletion, the double deletion of OSR/SPAK in OVLT caused polyuria with decreased urine osmolality that persisted in water restriction. Circulating levels of AVP and copeptin were increased by water restriction in control mice. In contrast, water restriction failed to increase the levels in OSR/SPAK-deletion mice. Knockdown of the Kv3.1 channel in OVLT by shRNA showed the central diabetes insipidus (DI) phenotype as well. Hypertonicity increased K+ currents and WNKs inhibitor prevented the increase in OVLT neurons. Conclusions: Mice with neuronal-specific OSR1/SPAK deletion have water homeostasis defects consistent with partial central DI; Evidence supporting that OSR1/SPAK acts downstream of WNK1 to regulate AVP release; WNK1-OSR1/SPAK activates Kv3.1 to increase firing frequency of neurons projecting from CVOs to PVN. Our findings reveal that an intracellular protein acts as a sensor for extracellular tonicity and provide fresh insights into the mechanisms by which the body maintains osmolality constancy. Future studies will investigate how OSR1/SPAK regulates Kv3.1 channels. NIDDK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of the median preoptic nucleus in the development of chronic deoxycorticosterone acetate (DOCA)-salt hypertension.

We have previously reported that the subfornical organ (SFO) does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the organum vasculosum of the lamina terminalis (OVLT) plays a significant role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Since efferent fibers of the OVLT project to and through the median preoptic nucleus (MnPO), the present study was designed to test the hypothesis that the MnPO is necessary for DOCA-salt hypertension in the rat. Male Sprague-Dawley rats underwent SHAM (MnPOsham; n = 5) or electrolytic lesion of the MnPO (MnPOx; n = 7) followed by subsequent unilateral nephrectomy and telemetry instrumentation. After recovery and during the experimental protocol, rats consumed a 0.1% NaCl diet and 0.9% NaCl drinking solution. Mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). The chronic pressor response to DOCA was attenuated in MnPOx rats by Day 11 of treatment and continued such that MAP increased 25 ± 3 mmHg in MnPOsham rats by Day 21 of DOCA compared to 14 ± 3 mmHg in MnPOx rats. These results support the hypothesis that the MnPO is an important brain site of action and necessary for the full development of DOCA-salt hypertension in the rat.

Effects of OVLT or MnPO lesion on the gut microbiome

Hypertension is a multifaceted condition affecting 700 million people worldwide, and despite decades of study, several aspects of its complex pathophysiology remain unclear. Changes in the gut microbiome have been associated with hypertension, though the cause and effect are not well defined. Historically, circumventricular organs in the brain, such as the organum vasculosum of the lamina terminalis (OVLT), and its central downstream nucleus the median preoptic nucleus (MnPO) have been shown to play a role in the pathogenesis of hypertension. Studies from our lab have demonstrated roles of both the OVLT and MnPO in the pathogenesis of angiotensin II mediated hypertension. Furthermore, we have previously reported that DOCA-salt treated OVLT lesioned rats had attenuated hypertension, and a gut microbial population more closely resembling normal controls, compared to sham lesioned rats. Lastly, we have recently shown the MnPO to be necessary in mediating DOCA-salt hypertension in the rat. Because data suggests changes in the gut microbiome occurred during the attenuated hypertensive response in lesioned animals, it is still unclear whether these changes occurred due to and shortly after the lesion, or subsequently during the hypertensive stimulus in lesioned animals. Therefore, the goal of this study was to further define the relationship between an OVLT or MnPO lesion and consequent changes in the gut microbiome without any hypertensive stimulus. Male Sprague Dawley rats underwent electrolytic lesion or sham operation using stereotaxic surgery with predetermined coordinates and settings. After 7 days, brain and regional gut tissues were harvested for analysis. Gut microbial genomic data from lesioned and sham rats were analyzed, and PCoA analysis showed statistically significant differences in microbiome composition between OVLT lesioned and sham rats in most gut regions. Generally, Shannon diversity analysis revealed sham rats had a more diverse population than OVLT lesioned rats, though both had a relatively similar spread of species abundance. Additionally, there was a common trend of higher relative abundance of Ligilactobacillus in lesioned rats for all four gut regions. In conclusion, the OVLT lesion itself has effects on the diversity of the gut microbiome, which suggest an OVLT-gut microbiome link that may contribute to attenuating hypertension. This study was supported by University of Minnesota Grant-In-Aid of Research, Artistry and Scholarship #546839 and a University of Minnesota Lillehei Heart Institute Collaborative Pilot Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute hyperosmotic stimulus of the Organum Vasculosum of the Lamina Terminalis leads to increase in the blood pressure dependent on release of ATP into the Paraventricular Nucleus of the Hypothalamus of rats

The neural network involved in hyperosmolality-induced hypertension includes the activation of the organum vasculosum of the lamina terminalis (OVLT) with monosynaptic connections to the paraventricular nucleus of the hypothalamus (PVN) that expresses an abundance of purinergic receptors including P2 receptors. Previously, we have shown that hyperosmotic-induced sympathoexcitation at the level of the PVN depends on the P2 receptors. More recently, we have shown that hyperosmotic stimulus induces the release of ATP in the PVN, at least in part, from astrocytes. Here we hypothesize that the increase in the blood pressure (BP) induced by acute hyperosmotic stimulus in the OVLT involves the release of ATP within the PVN neurons, acting on P2 receptors. Thus, we sought to determine (1) whether P2X7-expressing OVLT and PVN neurons are activated by hyperosmotic challenge, and (2) what effects P2 receptor antagonism on changes in the BP mediated by an acute hyperosmotic stimulus in the OVLT. Adult Wistar rats (10-12 weeks old; CEUA ICB/USP: #4895140819 and #1521230221) were used in two protocols: 1) Double-labeling immunofluorescence of P2X7 (anti-P2X7 receptor, 1:500) expressing neurons with FOS (anti-cfos, 1:3000) animals received i.v administration of hypertonic (NaCl, 3M, n=4) or isotonic saline (NaCl, 0.154M, n=4), followed by evaluation of immunostaining to FOS and P2X7 receptors in the OVLT and PVN; 2) OVLT-PVN microinjections and BP monitoring: under anesthesia rats (n=5), received catheters in the femoral vein and artery for the administration of urethane (1g/kg) and BP recording signals, respectively. Microinjections of 3M NaCl (50nL) were administered into the OVLT, before and after bilateral antagonism of P2 purinergic receptors (PPADS, 10uM-100nL on each side) in the PVN with simultaneous BP recording. Data were expressed as the mean ± SD, and statistical significance level of p<0.05 by Student’s T-test. Immunoreactive neurons for the P2X7 receptor subunit were observed in all compartments of the OVLT and PVN. Hyperosmotic stimulus significantly increased the number of Fos+ neurons in both the OVLT and PVN. While a small number of P2X7 receptors expressing OVLT and PVN neurons was observed in rats treated with isotonic saline, significantly more P2X7-expressing neurons expressed Fos+ in the OVLT with hypertonic saline. The stimulus of the OVLT with 3M NaCl elicited a significant increase in the BP. This effect was attenuated after bilateral injection of PPADS in the PVN (ΔMAP: NaCl OVLT:+10±1mmHg vs. NaCl OVLT post-PPADS PVN: +2.4±1.3mmHg, p<0.0001). Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X7 expressing OVLT and PVN neurons and that the elevation in the BP induced by hyperosmotic stimulus in the OVLT involves the endogenous release of ATP within the PVN, likely as part of the neural control of circulation during osmotic challenges. Financial Support: FAPESP #2019/19894-8, CAPES #88887.364432/2019-00. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats.

Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt-Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased the mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, the mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

Brain sodium sensing for regulation of thirst, salt appetite, and blood pressure.

The brain possesses intricate mechanisms for monitoring sodium (Na) levels in body fluids. During prolonged dehydration, the brain detects variations in body fluids and produces sensations of thirst and aversions to salty tastes. At the core of these processes Nax , the brain's Na sensor, exists. Specialized neural nuclei, namely the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which lack the blood-brain barrier, play pivotal roles. Within the glia enveloping the neurons in these regions, Nax collaborates with Na+ /K+ -ATPase and glycolytic enzymes to drive glycolysis in response to elevated Na levels. Lactate released from these glia cells activates nearby inhibitory neurons. The SFO hosts distinct types of angiotensin II-sensitive neurons encoding thirst and salt appetite, respectively. During dehydration, Nax -activated inhibitory neurons suppress salt-appetite neuron's activity, whereas salt deficiency reduces thirst neuron's activity through cholecystokinin. Prolonged dehydration increases the Na sensitivity of Nax via increased endothelin expression in the SFO. So far, patients with essential hypernatremia have been reported to lose thirst and antidiuretic hormone release due to Nax -targeting autoantibodies. Inflammation in the SFO underlies the symptoms. Furthermore, Nax activation in the OVLT, driven by Na retention, stimulates the sympathetic nervous system via acid-sensing ion channels, contributing to a blood pressure elevation.

Constitutive cell proliferation and neurogenesis in the organum vasculosum lamina terminalis and subfornical organ of adult rats.

Neurogenesis continues throughout adulthood in the subventricular zone, hippocampal subgranular zone, and the hypothalamic median eminence (ME) and the adjacent medio-basal hypothalamus. The ME is one of the circumventricular organs (CVO), which are specialized brain areas characterized by an incomplete blood-brain barrier and, thus, are involved in mediating communication between the central nervous system and the periphery. Additional CVOs include the organum vasculosum laminae terminalis (OVLT) and the subfornical organs (SFO). Previous studies have demonstrated that the ME contains neural stem cells (NSCs) capable of generating new neurons and glia in the adult brain. However, it remains unclear whether the OVLT and SFO also contain proliferating cells, the identity of these cells, and their ability to differentiate into mature neurons. Here we show that glial and mural subtypes exhibit NSC characteristics, expressing the endogenous mitotic maker Ki67, and incorporating the exogenous mitotic marker BrdU in the OVLT and SFO of adult rats. Glial cells constitutively proliferating in the SFO comprise NG2 glia, while in the OVLT, both NG2 glia and tanycytes appear to constitute the NSC pool. Furthermore, pericytes, which are mural cells associated with capillaries, also contribute to the pool of cells constitutively proliferating in the OVLT and SFO of adult rats. In addition to these glial and mural cells, a fraction of NSCs containing proliferation markers Ki67 and BrdU also expresses the early postmitotic neuronal marker doublecortin, suggesting that these CVOs comprise newborn neurons. Notably, these neurons can differentiate and express the mature neuronal marker NeuN. These findings establish the sensory CVOs OVLT and SFO as additional neurogenic niches, where the generation of new neurons and glia persists in the adult brain.

Insights into morphometry and topography of corpus callosum among Indians.

Corpus callosum is one of the major association fibre of brain performs an integral role of integration and communication of information between the two hemispheres. 50 formalin fixed cerebral hemispheres (25 right and 25 left) were used for the study. The longitudinal and vertical length of brain, longitudinal length and height of corpus callosum, distance of corpus callosum from various landmarks such as frontal and occipital pole, anterior commissure, lamina terminalis, and highest point on parietal pole and width of different parts of corpus callosum and height were measured. Results were analysed statistically. The results showed positive correlation between the longitudinal dimension of brain and all other parameters. Morphometric variation in size and its relation to nearby structures are seen in many neurological and psychiatric conditions such as Alzheimer's disease, Schizophrenia and bipolar disorders. Hence the present study can be used as reference by neurologist, neurosurgeons and psychiatrists.

Parallel neural pathways control sodium consumption and taste valence

The hedonic value of salt fundamentally changes depending on the internal state. High concentrations of salt induce innate aversion under sated states, whereas such aversive stimuli transform into appetitive ones under sodium depletion. Neural mechanisms underlying this state-dependent salt valence switch are poorly understood. Using transcriptomics state-to-cell-type mapping and neural manipulations, we show that positive and negative valences of salt are controlled by anatomically distinct neural circuits in the mammalian brain. The hindbrain interoceptive circuit regulates sodium-specific appetitive drive , whereas behavioral tolerance of aversive salts is encoded by a dedicated class of neurons in the forebrain lamina terminalis (LT) expressing prostaglandin E2 (PGE2) receptor, Ptger3. We show that these LT neurons regulate salt tolerance by selectively modulating aversive taste sensitivity, partly through a PGE2-Ptger3 axis. These results reveal the bimodal regulation of appetitive and tolerance signals toward salt, which together dictate the amount of sodium consumption under different internal states.

The Role of Cisternostomy and Cisternal Drainage in the Treatment of Aneurysmal Subarachnoid Hemorrhage: A Comprehensive Review.

Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension, hydrocephalus, cerebral vasospasm (CV), and delayed cerebral ischemia (DCI), which result in increased morbidity and mortality. During open microsurgical repair, cisternal access is achieved essentially to gain proximal vascular control and aneurysm exposition. Cisternostomy also allows brain relaxation, removal of cisternal clots, and restoration of the CSF dynamics through the communication between the anterior and posterior circulation cisterns and the ventricular system, with the opening of the Membrane of Liliequist and lamina terminalis, respectively. Continuous postoperative CSF drainage through a cisternal drain (CD) is a valuable option for treating acute hydrocephalus and intracranial hypertension. Moreover, it efficiently removes the blood and toxic degradation products, with a potential benefit on CV, DCI, and shunt-dependent hydrocephalus. Finally, the CD is an effective pathway to administer vasoactive, fibrinolytic, and anti-oxidant agents and shows promising results in decreasing CV and DCI rates while minimizing systemic effects. We performed a comprehensive review to establish the adjuvant role of cisternostomy and CD performed in cases of direct surgical repair for ruptured intracranial aneurysms and their role in the prevention and treatment of aSAH complications.

Evaluation of cellular activity in response to sleep deprivation by a comprehensive analysis of the whole mouse brain.

Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on neuronal activity in several brain regions have been identified, a comprehensive evaluation of the whole brain is still lacking. Hence, we performed SD using two different methods, gentle handling and a dedicated chamber, in targeted recombination in active populations 2 (TRAP2) mice crossed with Rosa-ZsGreen reporter mice and visualized cellular activity in the whole brain. Using the semi-automated post-imaging analysis tool Slice Histology Alignment, Registration, and Cell Quantification (SHARCQ), the number of activated cells was quantified. From the analysis of 14 brain regions, cellular activity was significantly increased in the olfactory areas and decreased in the medulla by the two SD methods. From the analysis of the further subdivided 348 regions, cellular activity was significantly increased in the vascular organ of the lamina terminalis, lateral hypothalamic area, parabigeminal nucleus, ventral tegmental area, and magnocellular reticular nucleus, and decreased in the anterior part of the basolateral amygdalar nucleus, nucleus accumbens, septohippocampal nucleus, reticular nucleus of the thalamus, preoptic part of the periventricular hypothalamic nucleus, ventromedial preoptic nucleus, rostral linear nucleus raphe, facial motor nucleus, vestibular nuclei, and some fiber tracts (oculomotor nerve, genu of corpus callosum, and rubrospinal tract) by the two SD methods. Two subdivided regions of the striatum (caudoputamen and other striatum), epithalamus, vascular organ of the lamina terminalis, anteroventral preoptic nucleus, superior colliculus optic layer, medial terminal nucleus of the accessory optic tract, pontine gray, and fiber tracts (medial lemniscus, columns of the fornix, brachium of the inferior colliculus, and mammillary peduncle) were differentially affected by the two SD methods. Most brain regions detected from these analyses have been reported to be involved in regulating sleep/wake regulatory circuits. Moreover, the results from the connectivity analysis indicated that the connectivity of cellular activity among brain regions was altered by SD. Together, such a comprehensive analysis of the whole brain is useful for understanding the mechanisms by which SD and/or sleep disruption affects brain function.

Central administered xenin induced Fos expression in nesfatin-1 neurons in rats

Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.

Hypotension and Bradycardia Following Papaverine Installation During Intracranial Aneurysm Surgery: A Report of Three Cases

Abstract Introduction One of the major complications of intracranial aneurysm surgery is vasospasm. Papaverine is an effective vasodilator that can be instilled directly onto the vessels in the operative field with the aim of preventing intraoperative and postoperative vasospasm. Several case reports of hemodynamic instability in general and of hypotension, in particular, were reported after the use of topical papaverine during aneurysm clipping surgery. Case description Herein, we report three cases of transient profound hypotension and relative bradycardia after intracisternal papaverine usage during ruptured anterior communicating artery aneurysm clipping surgery. Conclusion Caution should be taken while using papaverine intracisternally during anterior circulation aneurysm clipping, since it may cause several serious complications, including profound hemodynamic instability, particularly when instilling on a fenestrated lamina terminalis.