Hippocampal Vascular Supply and Its Role in Vascular Cognitive Impairment.

The incidence of age-related dementia is increasing as the world population ages and due to lack of effective treatments for dementia. Vascular contributions to cognitive impairment and dementia are increasing as the prevalence of pathologies associated with cerebrovascular disease rise, including chronic hypertension, diabetes, and ischemic stroke. The hippocampus is a bilateral deep brain structure that is central to learning, memory, and cognitive function and highly susceptible to hypoxic/ischemic injury. Compared with cortical brain regions such as the somatosensory cortex, less is known about the function of the hippocampal vasculature that is critical in maintaining neurocognitive health. This review focuses on the hippocampal vascular supply, presenting what is known about hippocampal hemodynamics and blood-brain barrier function during health and disease, and discusses evidence that supports its contribution to vascular cognitive impairment and dementia. Understanding vascular-mediated hippocampal injury that contributes to memory dysfunction during healthy aging and cerebrovascular disease is essential to develop effective treatments to slow cognitive decline. The hippocampus and its vasculature may represent one such therapeutic target to mitigate the dementia epidemic.

Electroacupuncture Relieves Hippocampal Injury by Heme Oxygenase-1 to Improve Mitochondrial Function.

INTRODUCTION: Electroacupuncture (EA) treatment has been demonstrated to have the potential to prevent sepsis-induced hippocampal injury; however, the mechanisms underlying the protective effects of EA against such injury remain unclear. Herein, to elucidate these mechanisms, we constructed a mouse model of lipopolysaccharide (LPS)-induced hippocampal injury to investigate the protection mechanism of EA and to determine whether heme oxygenase-1 (HO-1)-mediated mitochondrial function is involved in the protective effect of EA. MATERIALS AND METHODS: The sepsis model of hippocampal injury was induced by administering LPS. The Zusanli and Baihui acupoints were stimulated using EA for 30 min once a day, for 5 d before LPS exposure and the first day after administering LPS. Hippocampal injury was investigated by hematoxylin and eosin staining and Nissl staining. HO-1 levels were measured using Western blotting. Mitochondrial metabolism was validated by assessing adenosine triphosphate, superoxide dismutase, malondialdehyde levels, reactive oxygen species production, and mitochondrial respiratory chain activity. Mitochondrial morphology was analyzed by transmission electron microscopy. RESULTS: EA treatment alleviated neuronal injury, impeded oxidative stress, and improved mitochondrial respiratory function, energy metabolism, and mitochondrial morphology in LPS-exposed mice. In addition, HO-1 knockout aggravated LPS-induced hippocampal injury, aggravated oxidative stress, and reduced mitochondrial respiratory function and aggravated mitochondrial swelling, crest relaxation, and vacuole degeneration. Moreover, EA was unable to reverse the hippocampal damage and mitochondrial dysfunction caused by LPS exposure after HO-1 knockout. CONCLUSIONS: EA improves LPS-induced hippocampal injury by regulating HO-1-mediated mitochondrial function. Furthermore, HO-1 plays a critical role in maintaining mitochondrial function and resisting oxidative injury.

Hippocampal diffusion abnormality after febrile status epilepticus is related to subsequent epilepsy.

OBJECTIVE: To assess hippocampal signal changes on diffusion-weighted imaging (DWI) during the acute period after febrile status epilepticus (FSE) and to examine the relationship between DWI and subsequent epilepsy. METHODS: A prospective, multicenter study of children with a first episode of FSE was performed. The patients underwent magnetic resonance imaging (MRI) within 3 days of FSE, and signal intensity was evaluated on DWI. Electroencephalography studies within 3 days of FSE were also assessed. Nine to 13 years after FSE, information on subsequent epilepsy was obtained. RESULTS: Twenty-two children with FSE were evaluated. DWI showed unilateral hippocampal hyperintensity in six patients (27%). Three of six patients with hippocampal hyperintensity had ipsilateral thalamic hyperintensity. On EEG within 3 days of FSE, five of six patients with hippocampal hyperintensity had ipsilateral focal slowing, spikes, or attenuation. Nine to 13 years later, the outcomes could be determined in five patients with hippocampal hyperintensity and in 10 without. All 5 patients with hippocampal hyperintensity had hippocampal atrophy and developed focal epilepsy, whereas only 1 of 10 patients without hippocampal hyperintensity developed epilepsy (P = 0.002). Ictal semiology was concordant with temporal lobe seizures in all patients. Ipsilateral temporal epileptiform abnormalities were seen on EEG in four of five at last follow-up. SIGNIFICANCE: Acute DWI hippocampal hyperintensity was seen in 27% of patients with FSE. Acute DWI hyperintensity suggests cytotoxic edema caused by prolonged seizure activity. Hippocampal DWI hyperintensity is related to mesial temporal lobe epilepsy and can be a target of neuroprotective treatments to prevent the onset of epilepsy.

Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury.

OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1ß levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1ß and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1ß, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1ß or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).

Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. CLINICAL CASE: An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition, occasional focal areas of ischemic injury showing filiform neurons with reactive astrocytic gliosis background consistent with acute lesions were observed in CA3. CONCLUSIONS: Fat embolism should be considered a potential cause of sr-NCSE. This article is part of a Special Issue entitled "Status Epilepticus".

Qingzhuan dark tea Theabrownin alleviates hippocampal injury in HFD-induced obese mice through the MARK4/NLRP3 pathway.

Background: Feeding on a high-fat diet (HFD) results in obesity and chronic inflammation, which may have long-term effects on neuroinflammation and hippocampal injury. Theabrownin, a biologically active compound derived from the microbial fermentation of Qingzhuan dark tea, exhibits anti-inflammatory properties and lipid-lowering effects. Nevertheless, its potential in neuroprotection has yet to be investigated. Consequently, this study aims to investigate the neuroprotective effects of Theabrownin extracted from Qingzhuan dark tea, as well as its potential therapeutic mechanisms. Methods: Male C57 mice were subjected to an 8-week HFD to induce obesity, followed by oral administration of Theabrownin from Qingzhuan dark tea. Lipid levels were detected by Elisa kit, hippocampal morphological damage was evaluated by HE and Nissl staining, and the expression levels of GFAP, IBA1, NLRP3, MARK4, and BAX in the hippocampus were detected by immunofluorescence (IF), and protein expression levels of NLRP3, MARK4, PSD95, SYN1, SYP, and Bcl-2 were detected by Western Blot (WB). Results: Theabrownin treatment from Qingzhuan dark tea prevents alterations in body weight and lipid levels in HFD-fed mice. Furthermore, Theabrownin decreased hippocampal morphological damage and reduced the activation of astrocytes and microglia in HFD-fed mice. Moreover, Theabrownin decreased the expression of MARK4 and NLRP3 in HFD-fed mice. Besides, Theabrownin elevated the expression of PSD95, SYN1, and SYP in HFD-fed obese mice. Finally, Theabrownin prevented neuronal apoptosis, reduced the expression of BAX, and increased the expression of Bcl-2 in HFD-fed obese mice. Conclusions: In summary, our current study presents the first demonstration of the effective protective effect of Theabrownin from Qingzhuan dark tea against HFD-induced hippocampal damage in obese mice. This protection may result from the regulation of the MARK4/NLRP3 signaling pathway, subsequently inhibiting neuroinflammation, synaptic plasticity, and neuronal apoptosis.

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway.

Despite the observation of diabetes-induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high-fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl-2, BAX, and Cleaved-Caspase-3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase-12); NLRP3 inflammasome (NLRP3, ASC, and caspase-1); inflammatory cytokines (IL-18, IL-1ß, and TNF-α); AKT (P-AKT); and mitogen-activated protein kinase (MAPK) pathway (P-ERK, P-p38, and P-JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti-inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER-related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes-induced brain tissue damage and the associated disease.

Walk Locomotion Kinematic Changes in a Model of Penetrating Hippocampal Injury in Male/Female Mice and Rats.

Traumatic brain injury has been the leading cause of mortality and morbidity in human beings. One of the most susceptible structures to this damage is the hippocampus due to cellular and synaptic loss and impaired hippocampal connectivity to the brain, brain stem, and spinal cord. Thus, hippocampal damage in rodents using a stereotaxic device could be an adequate method to study a precise lesion from CA1 to the dentate gyrus structures. We studied male and female rats and mice, analyzing hindlimb locomotion kinematics changes to compare the locomotion kinematics using the same methodology in rodents. We measure (1) the vertical hindlimb metatarsus, ankle, and knee joint vertical displacements (VD) and (2) the factor of dissimilarity (DF). The VD in intact rats in metatarsus, ankle, and knee joints differs from that in intact mice in similar joints. In rats, the vertical displacement through the step cycle changed in the left and right metatarsus, ankle, and knee joints compared to the intact group versus the lesioned group. More subtle changes were also observed in mice. DF demonstrates contrasting results when studying locomotion kinematics of mice or rats and sex-dependent differences. Thus, a precise lesion in a rodent's hippocampal structure discloses some hindlimb locomotion changes related to species and sex. Thus, we only have a qualitative comparison between murine species. In order to make a comparison with other species, we should standardize the model.

TMAO promotes dementia progression by mediating the PI3K/Akt/mTOR pathway.

BACKGROUND: Dementia poses a serious threat to the daily and social abilities of patients, and trimethylamine-N-oxide (TMAO) is a metabolite of the gut microbiota involved in regulating the inflammatory response. However, the role of TMAO in dementia needs further investigation. This study aimed to investigate the effects and possible mechanisms of TMAO on dementia, which may provide ideas for the treatment of dementia. MATERIALS AND METHODS: Dementia mice were induced by D-galactose + AlCl3, and the changes in learning memory capacity, histopathology, inflammatory factors, and PI3K/Akt/mTOR in mice treated with TMAO were analyzed to determine the mechanism of TMAO action on dementia. In addition, the effect of TMAO+PI3K inhibitor treatment on mice was also analyzed to further determine the mechanism of TMAO effect on dementia. RESULTS: The results revealed that the dementia group had significantly higher TMAO levels and a significant hippocampal injury and inflammatory response. TMAO treatment promoted hippocampal injury and promoted the level of inflammatory cytokines. Further study of PI3K/Akt/mTOR signaling pathway showed that the expression of p-PI3K, p-Akt, and p-mTOR was significantly increased in the dementia group, and it was more obvious after TMAO treatment. And hippocampal injury, inflammatory response, and increase of p-PI3K, p-Akt, p-mTOR were reversed by TMAO+PI3K inhibitor. CONCLUSIONS: This study determined that TMAO promotes dementia through the PI3K/Akt/mTOR signaling pathway, suggesting that TMAO may be a potential target for dementia.

The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts.

Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.

Calpastatin Overexpression Protects against Excitotoxic Hippocampal Injury and Traumatic Spinal Cord Injury.

Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic mice that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (n = 5, p < 0.05). The PrP-hCAST mice (n = 13) displayed a significant improvement in locomotor function at one and three weeks after contusive SCI compared with the WT controls (n = 9, p < 0.05). Histological assessment of lesion volume and tissue sparing, performed on the same animals used for behavioral analysis, revealed that calpastatin overexpression resulted in a 30% decrease in lesion volume (p < 0.05) and significant increases in tissue sparing, white matter sparing, and gray matter sparing at four weeks post-injury compared with WT animals. Calpastatin overexpression reduced α-spectrin breakdown by 51% at 24 h post-injury, compared with WT controls (p < 0.05, n = 3/group). These results provide support for the hypothesis that sustained calpain-dependent proteolysis contributes to pathological deficits after excitotoxic injury and traumatic SCI.

Kinematic Changes in a Mouse Model of Penetrating Hippocampal Injury and Their Recovery After Intranasal Administration of Endometrial Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Locomotion speed changes appear following hippocampal injury. We used a hippocampal penetrating brain injury mouse model to analyze other kinematic changes. We found a significant decrease in locomotion speed in both open-field and tunnel walk tests. We described a new quantitative method that allows us to analyze and compare the displacement curves between mice steps. In the tunnel walk, we marked mice with indelible ink on the knee, ankle, and metatarsus of the left and right hindlimbs to evaluate both in every step. Animals with hippocampal damage exhibit slower locomotion speed in both hindlimbs. In contrast, in the cortical injured group, we observed significant speed decrease only in the right hindlimb. We found changes in the displacement patterns after hippocampal injury. Mesenchymal stem cell-derived extracellular vesicles had been used for the treatment of several diseases in animal models. Here, we evaluated the effects of intranasal administration of endometrial mesenchymal stem cell-derived extracellular vesicles on the outcome after the hippocampal injury. We report the presence of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, and interleukin 6 in these vesicles. We observed locomotion speed and displacement pattern preservation in mice after vesicle treatment. These mice had lower pyknotic cells percentage and a smaller damaged area in comparison with the nontreated group, probably due to angiogenesis, wound repair, and inflammation decrease. Our results build up on the evidence of the hippocampal role in walk control and suggest that the extracellular vesicles could confer neuroprotection to the damaged hippocampus.

Osteopontin-Enhanced Autophagy Attenuates Early Brain Injury via FAK-ERK Pathway and Improves Long-Term Outcome after Subarachnoid Hemorrhage in Rats.

Osteopontin (OPN) enhances autophagy, reduces apoptosis, and attenuates early brain injury (EBI) after a subarachnoid hemorrhage (SAH). A total of 87 Sprague-Dawley rats were subjected to sham or SAH operations to further investigate the signaling pathway involved in osteopontin-enhanced autophagy during EBI, and the potential effect of recombinant OPN (rOPN) administration to improve long-term outcomes after SAH. Rats were randomly divided into five groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), SAH + rOPN (5 µg/rat recombinant OPN), SAH + rOPN + Fib-14 (30 mg/kg of focal adhesion kinase (FAK) inhibitor-14), and SAH + rOPN + DMSO (dimethyl sulfoxide). Short-term and long-term neurobehavior tests were performed, followed by a collection of brain samples for assessment of autophagy markers in neurons, pathway proteins expression, and delayed hippocampal injury. Western blot, double immunofluorescence staining, Nissl staining, and Fluoro-Jade C staining assay were used. Results showed that rOPN administration increased autophagy in neurons and improved neurobehavior in a rat model of SAH. With the administration of FAK inhibitor-14 (Fib-14), neurobehavioral improvement and autophagy enhancement induced by rOPN were abolished, and there were consistent changes in the phosphorylation level of ERK1/2. In addition, early administration of rOPN in rat SAH models improved long-term neurobehavior results, possibly by alleviating hippocampal injury. These results suggest that FAK-ERK signaling may be involved in OPN-enhanced autophagy in the EBI phase after SAH. Early administration of rOPN may be a preventive and therapeutic strategy against delayed brain injury after SAH.

The hippocampus facilitates integration within a symbolic field.

This paper attempts to elaborate a fundamental brain mechanism involved in the creation and maintenance of symbolic fields of thought. It will integrate theories of psychic spaces as explored by Donald Winnicott and Wilfred Bion with the neuroscientific examinations of those with bilateral hippocampal injury to show how evidence from both disciplines sheds important light on this aspect of mind. Possibly originating as a way of maintaining an oriented, first person psychic map, this capacity allows individuals a dynamic narrative access to a realm of layered elements and their connections. If the proposed hypothesis is correct, the hippocampus facilitates the integration of this symbolic field of mind, where narrative forms of thinking, creativity, memory, and dreaming are intertwined. Without the hippocampus, there is an inability to engage many typical forms of thought itself. Also, noting the ways these individuals are not impaired supports theories about other faculties of mind, providing insight into their possible roles within human thought. The evidence of different systems working in conjunction with the symbolic field provides tantalizing clues about these fundamental mechanisms of brain and mind that are normally seamlessly integrated, and hints at future areas of clinical and laboratory research, both within neuroscience and psychoanalysis.

Hippocampal signal abnormality on the first day of illness in acute encephalopathy with biphasic seizures and late reduced diffusion caused by HHV-6 infection.

We report a 13-month-old girl who developed acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with transient reduced diffusion in the hippocampus and anterior commissure on diffusion-weighted imaging (DWI), which was performed on the first day after febrile status epilepticus (FSE) as the initial neurological symptom of AESD. DWI just after late seizures showed high signal intensity lesions in both left hippocampus and anterior commissure, and left extratemporal and occipital subcortical white matter. HHV-6 DNA was positive in both blood and cerebrospinal fluid samples. DWI at two months after onset showed atrophy in the left mesial temporal lobe and extratemporal and occipital lobe without the signal abnormalities. Although it has been reported that magnetic resonance images tend to show no acute abnormality during the first two days in typical AESD, transient reduced diffusion could be found on the DWI performed on the first day of AESD.

Cognitive Dysfunction and Hippocampal Damage Induced by Hypoxic-Ischemic Brain Injury and Prolonged Febrile Convulsions in Immature Rats.

OBJECTIVE: Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children. METHODS: A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9. RESULTS: The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss. CONCLUSION: Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS.

Evaluation of hippocampal injury and cognitive function induced by embolization in the rat brain.

Embolism is responsible for at least 20% of all stroke and half of cerebral infarctions. A number of animal models have been developed to mimic thromboembolic stroke. However, little aimed directly at hippocampal damage and cognitive function. In the present study, three sizes of emboli (150-178 µm, 74-124 µm, and 48-74 µm) were employed to induce thromboembolic stroke model in rats. Results showed that the diameter of the particle was critical for animal behavioral and histopathological consequences. Hematoxylin-eosin (HE) staining revealed that CA1 and CA2-3, which are two of the main hippocampal subdivisions were injured seriously, especially induced by emboli(48-74 µm) . At 24 hr, the neurological deficit scores showed that emboli injection could cause significant neurological deficit, and the increase of neurological deficit scores correlated well to the diameter of emboli. At 60 days, emboli(150-178 µm) and emboli(48-74 µm) lead to obvious cognitive impairment, which correlated well to the hippocampal CA1 injury. Our research might be helpful to choose suitable size of emboli to induce animal model to research subcortical ischemia and vascular dementia. However, cognitive alterations and cerebral injury following different sizes of emboli injection in rats remains a topic for future investigation.