Long-Term Effects of Experimental Carotid Stenosis on Hippocampal Infarct Pathology, Neurons and Glia and Amelioration by Environmental Enrichment

Hippocampal atrophy and pathology are common in ageing-related disorders and associated with cognitive impairment and dementia. We explored whether environmental enrichment (EE) ameliorated the pathological sequelae in the hippocampus subsequent to chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS). Seventy-four male C57BL/6 J mice underwent BCAS or sham surgery. One-week after surgery, mice were exposed to three different degrees of EE; either standard housing conditions (std), limited 3-hour exposure to EE per day (3h) or full-time exposure to EE (full) for 3 months. Four months after surgery, the hippocampus was examined for the extent of vascular brain injury and neuronal and glial changes. Results showed that long-term BCAS induced strokes, most often in CA1 subfield, reduced 40-50% CA1 neurons (P<0.01) and increased microglia/macrophage in CA1-CA3 subfields (P<0.02). Remarkably, both 3h and full-time EE regimes attenuated hippocampal neuronal death and repressed recurrent strokes with complete prevention of larger infarcts in mice on full-time EE (P<0.01). Full-time EE also reduced astrocytic clasmatodendrosis and microglial/macrophage activation in all CA subfields. Our results suggest that exposure to EE differentially reduces long-term hypoperfusive hippocampal damage. The implementation of even limited EE may be beneficial for patients diagnosed with vascular cognitive impairment

Computer-Aided Automated Detection of Gene-Controlled Social Actions of Drosophila

Gene expression of social actions in Drosophilae has been attracting wide interest from biologists, medical scientists and psychologists. Gene-edited Drosophilae have been used as a test platform for experimental investigation. For example, Parkinson's genes can be embedded into a group of newly bred Drosophilae for research purpose. However, human observation of numerous tiny Drosophilae for a long term is an arduous work, and the dependence on human's acute perception is highly unreliable. As a result, an automated system of social action detection using machine learning has been highly demanded. In this study, we propose to automate the detection and classification of two innate aggressive actions demonstrated by Drosophilae. Robust keypoint detection is achieved using selective spatio-temporal interest points (sSTIP) which are then described using the 3D Scale Invariant Feature Transform (3D-SIFT) descriptors. Dimensionality reduction is performed using Spectral Regression Kernel Discriminant Analysis (SR-KDA) and classification is done using the nearest centre rule. The classification accuracy shown demonstrates the feasibility of the proposed system

Theories and Concepts

This chapter provides an overview of the existing theories on declarative memory and the hippocampal complex. In particular, theories/models of hippocampal functioning and declarative memory (i.e., the Standard Model of Consolidation, the Spatial Map Theory, the Relational Theory, the Multiple Trace Theory, the Dual-Process Theory, and the Perceptual-Mnemonic Feature Conjunction Model) were combined into a comprehensive unified framework. It is shown that these theories cannot fully explain the findings from empirical studies that examine the role of the medial temporal lobe in declarative memory. Therefore, this chapter tries to integrate the findings reported in the literature into a comprehensive unified framework of recognition and recall. This model not only considers long-term memory and the medial temporal lobe but also its relations with the prefrontal cortex and working memory

Phosphodiesterase Inhibitors in Object Recognition and Object Location Memory Tests

Phosphodiesterase (PDE) inhibitors prevent hydrolyzation of the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate; they are considered promising cognitive enhancers. Object recognition and object location tests contributed significantly to the advancement of current research on PDE inhibitors in memory, ageing and Alzheimer's disease research studies

Anti-convulsant Effects of Bongardia chrysogonum L. Tuber in the Pentylenetetrazole-induced Seizure Model

Background and Objective: The dried tuber of Bongardia chrysogonum (L.) is a popular folk remedy for its use in the treatment of epilepsy in traditional medicine. The study aimed to evaluate the anti-oxidant and anti-convulsant activity of B. chrysogonum ethanolic-aqueous extract using the Pentylenetetrazole (PTZ) kindling animal model. Materials and Methods: Male mice were randomly selected and divided into 9 experimental groups including: Control group, pentylenetetrazole kindled mice, positive mice group receiving valproate (200 mg kg–1 p.o.) a classic anticonvulsant drug and 3 groups receiving B. chrysogonum tuber-ethanolic or aqueous extract at a doses of (600, 900 and 1200 mg kg–1 p.o.). All groups, except the control, were kindled by 11 injections of PTZ (40 mg kg–1, i.p.). All groups, except the control group, were tested at 12th PTZ challenge dose (75 mg kg–1 i.p.). The exhibited phases of seizure (0-6) were observed and noted; moreover, anti-oxidant effect of these extract was examined in in vitro study by using a spectrophotometric technique. The significance of differences between groups were determined using one-way analysis of variance (ANOVA) followed by post hoc test, Dunnett’s multiple comparison tests. Results: The data showed that both valproate and B. chrysogonum tuber extracts delay the onset of convulsions, decrease duration of the seizure and reduced mortality significantly (p<0.05). In addition, B. chrysogonum showed a wide range of scavenging capacities for free radicals, which may underpin the effective in vivo seizure suppression. Conclusion: It was concluded that B. chrysogonum L. tuber extracts display anti-oxidant, free radical scavenging properties in vitro and, in mice, provides new scientific evidence for the anti-seizure properties of B. chrysogonum

Glutamate Signalling in Object Novelty Recognition Memory Tests

The object recognition and to a lesser extent the object location tests contributed to the better understanding of the role of glutamatergic signalling in memory. Pharmacological manipulation of glutamate signalling showed that its different components contribute to distinct stages of memory formation. Additionally positive modulation of glutamate transmission was shown to facilitate storage of object recognition memory, while its inhibition could be neuroprotective against excitotoxicity

Votucalis, a Novel Centrally Sparing Histamine-Binding Protein, Attenuates Histaminergic Itch and Neuropathic Pain in Mice

Votucalis is a biologically active protein in tick (R. appendiculatus) saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host’s immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H1 and H2 receptors as well as central histamine H4 receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions

Carotid Artery Disease in Post-Stroke Survivors and Effects of Enriched Environment on Stroke Pathology in a Mouse Model of Carotid Artery Stenosis

AIMS: Carotid artery disease (CAD) is an important risk factor for stroke. We first evaluated CAD and stroke pathology in elderly post-stroke survivors. To simulate CAD, we assessed long-term consequences of bilateral common carotid artery stenosis (BCAS) in mice and exposed them to environmental enrichment (EE). METHODS: Histopathological methods were used to determine degrees of CAD (% area stenosis), brain infarct types, sizes and distribution in post-stroke survivors and BCAS mice. Adult male C57BL/6J mice after BCAS or sham surgery were randomly assigned to standard housing (Std) or limited (3hrs) or full-time (Full) exposure to EE per day for 12 weeks. RESULTS: High frequencies of moderate carotid artery stenosis (51-75%) were evident in post-stroke survivors whereas those with severe CAD (>75% stenosis) exhibited greater numbers of cortical rather than subcortical infarcts and, were at higher risk of developing dementia. BCAS in mice reduced cerebral blood flow by 52% (P50% in BCAS mice exposed to EE compared with BCAS-Std (P<0.01). Frontal lobe and cortical strokes were associated with worsening working memory tested in a radial maze paradigm. Proteomic analysis revealed EE, both BCAS-3hrs and BCAS-Full attenuated coagulation cascade factors including fibrinogen and von Willebrand factor, markers of blood-brain barrier damage. CONCLUSION: Small cortical and subcortical infarcts were evident in both post-stroke survivors with CAD and BCAS mice. Experimental evidence suggested that moderate exposure to EE is sufficient to reduce subsequent stroke lesions