Deep Cortex Research Articles

Deep brain and motor cortex stimulation.

Deep brain stimulation (DBS) and motor cortex stimulation (MCS) are established surgical modalities that have been successfully used over the last several decades for treatment of numerous chronic pain disorders. Most often, these approaches are reserved for severe, disabling, and medically refractory syndromes after less invasive approaches have been tried and have failed. Although the exact mechanism of action for DBS and MCS remains unknown, it appears that these central neuromodulation processes have multifactorial effects on central pain processing and descending pain inhibition. Clinical studies and laboratory reports have shed some light on stimulation details and optimal parameters, as well as the choice of stimulation targets, best surgical indications, and expected long-term outcomes. Based on the worldwide published experience, it appears that additional data is needed to obtain regulatory approval for both MCS and DBS for the treatment of pain. Following approval, further clinical research will shape the ability to initiate, implement, and update comprehensive patient and procedure selection paradigms.

Diffuse Glomerular Nodular Lesions in Diabetic Pigs Carrying a Dominant-Negative Mutant Hepatocyte Nuclear Factor 1-Alpha, an Inheritant Diabetic Gene in Humans

Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α) P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3) gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI) with advanced glycation end-product (AGE) and N ε-carboxymethyl-lysine (CML) deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β) was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the somewhat acute and constitutive formation of nodules in this mammalian model might provide information facilitating identification of the principal mechanism underlying diabetic nodular sclerosis.

Porcine Melanotic Cutaneous Lesions and Lymph Nodes

Porcine melanomas have proven interesting in a wider biological perspective due to a common phenomenon of spontaneous regression, which is characterized by infiltration of macrophages, among others. Separation of neoplastic melanocytes from pigment-laden macrophages may, however, be challenging as the morphology of melanocytes varies considerably and sometimes resembles macrophages. The aim of this study was correspondingly to characterize and differentiate the cells in 20 porcine melanocytomas and regional lymph nodes by histologic examination and immunohistochemistry for melan A, PNL2, S100, lysozyme, alpha-1-antitrypsin, and ionized calcium binding adaptor molecule 1 (Iba1). Grossly, the melanocytomas were divided into 2 distinct types: pigmented maculae (n = 7) and raised tumors (n = 13). In the maculae, the pigmented cells were mainly melanocytes reactive for melan A, PNL2 and S100. In contrast, the majority of the cells in the raised tumors were melanophages, which expressed Iba1, alpha-1-antitrypsin, and lysozyme. Yet, cells histomorphologically indistinguishable from the melanophages expressed melan A and PNL2. These cells were Iba1 and S100 negative, and ultrastructurally, they were devoid of lysosomal bodies and filled with stage III and IV melanosomes. In the regional lymph nodes, melanocytes were present in the trabecular sinuses. In focally or diffusely black lymph nodes, pigmentation was, however, mainly due to aggregates of melanophages, which were confined to the trabeculae, deep cortex, and peripheral lymphoreticular tissue. Normal and neoplastic porcine melanocytes express melan A and PNL2, and immunohistochemical staining for melan A, PNL2, and Iba1 was found useful to identify and distinguish melanocytes and melanophages in porcine melanotic lesions.

Two cases of multinodular and vacuolating neuronal tumour

An unusual multinodular and vacuolating neuronal tumour (MVNT) has been described in the cerebral hemispheres of ten patients with adult-onset seizures. We report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic.

Chapter 14 - Affective Brain Areas and Sleep-Disordered Breathing

The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing, found in obstructive sleep apnea, heart failure, and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude-distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, caudal raphé, ventrolateral medulla, portions of the basal ganglia and, in CCHS, the locus coeruleus. Caudal raphé and locus coeruleus injury have the potential to modify serotonergic and adrenergic modulation of upper airway and arousal characteristics, as well as affective drive to breathe. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several of the affected rostral sites mediate aspects of dyspnea, especially in CCHS, while others participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation.

Absence of amyloid-beta in lenses of Alzheimer patients: A confocal Raman microspectroscopic study

We have compared the protein profiles in plaques and tangles in the hippocampus of post-mortem Alzheimer brains and in opaque and clear regions in the deep cortex of eye lenses of the same donors. From the 7 Alzheimer donors studied, 1 had pronounced bilateral cortical lens opacities, 1 moderate and 5 only minor or no cortical opacities. We focused on beta-sheet levels, a hallmarking property of amyloid-beta, the major protein of plaques and tau protein, the major protein of tangles in Alzheimer brains. Confocal Raman microspectroscopy and imaging was used in combination with hierarchical cluster analysis. Plaques and tangles show high levels of beta-sheets with a beta-sheet to protein ratio of 1.67. This ratio is 1.12 in unaffected brain tissue surrounding the plaques and tangles. In the lenses this ratio is 1.17 independently of the presence or absence of opacities. This major difference in beta-sheet conformation between hippocampus and lens is supported by Congo red and immunostaining of amyloid-beta and tau which were positive for plaques and tangles in the hippocampus but fully negative for the lens irrespective of the presence or absence of opacities. In line with a previous study (Michael et al., 2013) we conclude that cortical lens opacities are not typical for Alzheimer patients and are not hallmarked by accumulation of amyloid-beta, and can thus not be considered as predictors or indicators of Alzheimer disease as claimed by Goldstein et al. (2003).

Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats

Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption of flavonoid-rich foods and prevention of human disease including neurodegenerative disorders has been demonstrated. We assessed the effect of rutin (3,3′,4′,5,7-pentahydroxyflavone-3-rhamnoglucoside) on the mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in rats injected with β-amyloid (Aβ), which is implicated to have an important role in Alzheimer's disease (AD). Aβ was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected (i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100mg/kg) significantly increased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hippocampus of the rutin group was significantly lower than those in the control group. The content of sulfhydryl groups in the rutin group was higher than that in the control group. The findings show a possibility that rutin may have beneficial effects against neurotoxicity of Aβ on memory in rats.

Overdiagnosis: Under-recognized clinical and pathological features of “focal ischemic glomerulosclerosis clustering”

“Focal ischemic glomerulosclerosis clustering (FIGSC)” is a term used by us temporarily to describe a rare kind of focal renal scar with a high percentage of global sclerosis in the renal biopsy tissue. We retrospectively studied the clinical and pathological data from 15 cases of FIGSC followed up in order to avoid overdiagnosis and to investigate its diagnostic basis. We found that in 7 cases with FIGSC, the percentage of global sclerosis was higher than 50% with mild or moderate tubulointerstitial lesions, and most cases showed sclerotic regions distributed both beneath the renal capsule and in the deep cortex. Fourteen cases of afferent arterioles sclerosis were observed. Fourteen did not evolve to end-stage renal disease (ESRD) during the follow-up period. The values of the percentage of severe tubulointerstitial lesion, SCr, BUN, and the cumulative incidence of ESRD were significantly lower compared to the diffuse proliferative sclerosis glomerulonephritis group (P<0.05). The results suggest that the essence of FIGSC may be a kind of focal renal scar related to sclerosis, stenosis or obstruction of several adjacent afferent arterioles, not caused by original glomerulonephritis. Comprehensive understanding should be very important to avoid overdiagnosis and overtreatment.

The conundrum of protection from AKI by adenosine in rodent clamp ischemia models

Kim et al. show that isoflurane uses a tubule-based transforming growth factor-β/CD73-dependent process that generates adenosine to protect mice from ischemic acute kidney injury (AKI) with effects to prevent the 'no-reflow phenomenon' and decrease inflammation. While direct cytoprotection occurred in culture, extensive research suggests that in vivo adenosine protection from rodent ischemic AKI is mediated by a mutually cooperative mechanism involving blood flow, inflammation, and innate immunity through multiple adenosine receptors with promiscuous actions on diverse cell types.

Upregulation of prolactin receptor in proximal tubular cells was induced in cardiac dysfunction model mice

In order to clarify the interaction between cardiac dysfunction and sodium homeostasis in the kidney, we used a murine model of cardiac dysfunction and investigated the effect on sodium transporters in renal tubular cells. Cardiac function was deteriorated by abdominal aortic banding, and the gene expression of sodium transporters in the kidneys was evaluated by real-time RT-PCR and compared with that in the kidneys of control mice. Gene expression of all three variants of the murine prolactin receptor was enhanced by aortic banding. Upregulated prolactin receptor was distributed in the proximal tubular cells of the pars recta in the deep inner cortex and the outer stripe of the outer medulla. Prolactin has been reported to be a natriuretic hormone that inhibits proximal tubular Na(+)/K(+)-ATPase activity, resulting in reduced sodium reabsorption and the acceleration of natriuresis. Inhibition of endogenous prolactin secretion by bromocriptine administration decreased the urine sodium excretion in both aortic banding and control mice. On the other hand, excess exogenous prolactin administration enhanced urine potassium excretion in aortic banding mice. Furthermore, a high-sodium diet accelerated urinary sodium excretion, which was also significantly decreased by inhibition of endogenous prolactin secretion in aortic banding mice. We reported that the prolactin receptor was upregulated by aortic banding treatment. Prolactin-prolactin receptor interaction in the proximal tubular cells of the pars recta should involve a different mechanism of kaliuresis other than inhibition of Na(+)/K(+)-ATPase.

Histotopographical characterization of the para-aortic lymph nodes in the area near the origin of the thoracic duct, and its relationship to nodal cancer metastasis.

Using 10 elderly cadavers without macroscopically evident tumors, we histologically examined 115 para-aortic lymph nodes located near the origin of the thoracic duct after preparation of en bloc specimens using a clearance method. The afferent and efferent sides of these nodes were usually not discriminated clearly because i) the superficial cortex (B-lymphocyte area) and deep cortex (T-lymphocyte area) were not clearly differentiated due to lack of a typical hilus, and both cortices were intermingled to form “nodular masses”; ii) each nodule with a lining of macrophages was surrounded by dilated intermediate and subcapsular sinuses; iii) the nodes were often surrounded by multiple tributaries of the thoracic duct. Moreover, the nodes sometimes involved these tributaries inside. Therefore, the nodal architecture seemed to accelerate intranodal shunt flow without filtration through the cortex. Valves of the lymphatic vessel tended to be restricted to an area immediately before drainage into the thoracic duct. Thus, lymph flow was likely to change along a network of tributaries around a node. These morphologies suggested very limited barrier function of the para-aortic node against cancer metastasis. However, we hypothesized that “better” or “worse” types of nodes are histologically identifiable when they are picked up surgically along with the surrounding tissues.

Attenuated contractility in afferent arterioles during development of proteinuria in two‐kidney, one‐clip hypertensive rats

AimsWe wanted to investigate the contractile properties of afferent arterioles (AAs) from two‐kidney, one‐clip (2K1C) hypertensive rats before and during development of proteinuria, and whether these vessels behave differently in outer and inner renal cortex.MethodsWistar rats were subjected to either a 2K1C or sham operation. Blood pressure was measured and urine was sampled before the rats were killed after 18 ± 4 weeks. AAs were isolated from outer and inner renal cortex of the non‐clipped kidney of the 2K1C and from both kidneys of the sham rats with the agarose infusion technique. The AAs were stimulated with angiotensin II (AngII) in increasing concentrations (10−10 M to 10−7 M), and degree of contraction was recorded.ResultsThe preliminary results are based on AAs isolated from 9 rats (Sham: 3, 2K1C without proteinuria (2K1C Prot−): 2, and 2K1C with proteinuria (2K1C Prot+): 4). There was no difference in mean arterial pressure between the 2K1C with and without proteinuria (184 ± 6 vs. 178 ±8 mmHg, NS).We found a significantly attenuated response to AngII 10−7 M in the superficial AAs from both hypertensive groups compared to sham. However, in the AAs from the juxtamedullary nephrons there was a preserved response in the vessels from the 2K1C rats without proteinuria.ConclusionLoss of contractile properties of AAs in deep cortex may contribute to development of renal damage and proteinuria in this model.

3:46 PM Abstract No. 218 - ■ FEATURED ABSTRACTTargeting and recanalization with rapidly resorbable microspheres versus gelatin sponge particles in a pig kidney model

Purpose Resorbable embolization microspheres (REM) must have a time of resorption quick enough to provide a functional recanalization, and to avoid chronic vascular remodeling. We synthesized calibrated REM that resorbed in less than 24 hours and evaluated the performances of REM of 3 sizes (300-500μm, 500-700μm, and 700-900μm) in terms of targeting and recanalization, by comparison to handcut 1mm gelatin sponge particles (GSP). Materials and Methods Eight pigs underwent polar renal artery embolization with either REM of the 3 sizes or GSP. Angiograms were recorded before embolization, 10 minutes and before pig sacrifice 1 week after embolization. On each angiogram, the number of opacified segments of arteries at each bifurcation level was quantified. We analyzed the partition of the opacified segments and determined the level of occlusion, the percentage of occlusion and the recanalization rate for each product. In pathology, the distribution of GSP was assessed. Results REM 300-500μm occluded distal vessels, in interlobular arterioles in the deep cortex. REM 500-700μm and 700-900μm located more proximally, in the junctional arteries which are anastomotic arteries located at the junction between medulla and cortex. GSP occluded the interlobar arteries, proximally. At D7, recanalization rate of the larger REM was 105%, whereas for the two smaller sizes (500-700μm and 300-500μm) it was respectively 62% and 57%. GSP recanalized at 79%. Conclusion Embolizations with calibrated REM were successful and enabled a precise targeting of the occlusion. REM of different sizes targeted different levels of occlusion in kidney arteries. Within less than one week REM were completely resorbed, left no residual material and inflammation and the arteries recanalized between 60% and 100%. By comparison, handcut GSP provided a variable level of occlusion without actual targeting. They were partly degraded and accompanied by a foreign body reaction and the recanalization rate was important but never complete.

Rice protein ameliorates the progression of diabetic nephropathy in Goto–Kakizaki rats with high-sucrose feeding

The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto-Kakizaki (GK) rats was investigated.GK rats at 7 weeks of age were fed 20% RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol,TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P<0·05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P<0·05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P<0·05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P<0·05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.

New material of Pachyarmatherium from the late Pleistocene of northeastern Brazil: insights into its morphology and systematics

A study of recently collected and other undescribed material of Pachyarmatherium brasiliense from the State of Pernambuco, Brazil, was performed, and its type material was revised, improving our understanding of this species and providing additional information on its affinities. Two fused osteoderms representing the posteriormost osteoderm row of the pectoral buckler are described for the first time in the Pachyarmatherium. Several additional specimens included buckler, border, and at least one caudal osteoderm. The relationships of Pachyarmatherium have been subject to different interpretations. We propose that the presence of some osteoderm features suggests a closer affinity with Dasypodinae/cf. Dasypodini armadillos. A key feature supporting this conclusion is the presence of complementary small figures in adjoining buckler osteoderms of Pachyarmatherium, indicating that a single scale covered portions of three contiguous osteoderms. Other features observed are related to the histological microstructure, which includes a central cortex characterized by a poorly developed cancellous bone and a deep cortex with mineralized collagen fiber bundles that are oriented roughly parallel to the deep osteoderm surface. Likewise, these histological features support its exclusion from glyptodonts and pampatheres, which show a different histological arrangement in their osteoderms.

Subnetwork selection in deep cortical layers is mediated by beta-oscillation dependent firing

GENERAL COMMENTARY article Front. Syst. Neurosci., 24 June 2013 | https://doi.org/10.3389/fnsys.2013.00025

Cognitive Deficits and Delayed Neuronal Loss in a Mouse Model of Multiple Microinfarcts

Microinfarcts are a common clinical feature of the aging brain, particularly in patients with cognitive decline or vascular or Alzheimer's dementia. However, the natural history of these lesions remains largely unexplored. Here we describe a mouse (C57BL/6J) model of multiple diffuse microinfarcts induced by unilateral internal carotid artery injection of cholesterol crystals (40-70 μm). Microinfarcts were spread throughout the deep cortex, subcortical tissue, and hippocampus and were comprised of a core positive for CD68 (a marker for reactive microglia and macrophages), surrounded by large regions of glial fibrillary acidic protein-positive reactive astrogliosis. Widespread reactive gliosis, including mislocalization of the astrocytic water channel aquaporin 4 persisted long after injury, recovering only after 1 month after stroke. Within the cortex, neuronal cell death progressed gradually over the first month, from ∼35% at 3 d to 60% at 28 d after stroke. Delayed demyelination was also observed in lesions, beginning 28 d after stroke. These findings demonstrate that microinfarct development follows a distinct course compared to larger regional infarcts such as those induced by middle cerebral artery occlusion. The long-lasting gliosis, delayed neuronal loss, and demyelination suggest that the therapeutic window for microinfarcts may be much wider (perhaps days to weeks) than for larger strokes.

The spectrum of disease in chronic traumatic encephalopathy

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

7 T MRI reveals diffuse iron deposition in putamen and caudate nucleus in CADASIL

ObjectiveDiffuse iron deposition in the brain is commonly found in older people. One of the possible mechanisms that contribute to this iron deposition is cerebral small vessel disease. The aim...

Scanning Electron Microscopic Study of the Vascular System in the Hemal Node of the Bovine Cervical Region

The vasculature of the hemal node (HN) from the bovine cervical region was investigated using a combination of vascular corrosion casting and scanning electron microscopy. A dense vessel network of capsule was found surrounding the cast of HN parenchyma and had no connection with the subcapsular sinus; these vessels converged and exited the HN via the hilar vein. Within the HN, many anastomoses were found between the capillary networks and the surrounding sinuses in the follicular zone and deep cortex. The sinusoid pathway in the HN was characterized by subcapsular sinuses, which were continuous with the trabecular sinuses and tubular sinuses over the parenchyma, and these sinuses finally entered the medullary veins. In our study, direct communications between cortical capillaries and subcapsular sinuses were identified. This may explain the origin of numerous erythrocytes in the HN sinusoids and help to understand lymphocyte migration of the HN.