Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension.

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.

Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty.

There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in "paired viewing" experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had "object fields"); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition-related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

No spatial working memory deficit in beta-amyloid-exposed rats. A longitudinal study.

Two experiments are described assessing whether long-term intraventricular or intrahippocampal administration of beta-amyloid protein 1-40 (beta A1-40) affects spatial working memory in rats monitored in a longitudinal study using the open-field water maze. A delayed matching-to-position procedure (DMTP) was employed in which platform locations were semi-randomly altered between days but were kept constant over the four trials on each day. Intertrial intervals (ITIs) were either 30 s or 1 h between Trials 1 and 2 (all other intervals = 30 s), with Trial 2 performance being an index for spatial working memory. Animals were trained before and tested repeatedly at various intervals after application of various compounds (see below) in five successive test sessions (TSs). In Experiment 1, beta A1-40 was applied after a challenge with long-term oral exposure to aluminium (Al; as 0.1% sulfate in drinking water). This in itself did not affect spatial working memory at any delay, despite of the more than 6 months of intake. beta A1-40 administered alone via intracerebroventricular (icv) minipumps (20 micrograms in 250 microliters) led to a small increase in latencies to find the platform, which recovered to control levels 3 months after minipumps were exhausted. Application of beta A1-40 in Al-exposed animals led to a subtle and progressive decline in working memory. This deterioration was reversed by the nootropic compound nefiracetam, which had no effect on the Al only group. In Experiment 2, well-trained rats were bilaterally implanted with intra-hippocampal minipumps containing beta A1-40 or reverse sequence beta A40-1. This did not impair spatial working memory in the DMTP task, measured either directly after minipumps were exhausted, or 2 weeks later. When intraperitoneally (i.p.) injected with a low concentration of the muscarinic antagonist scopolamine (0.2 mg/kg), a dose that was not effective alone, animals in the beta A1-40 group were amnesic. These data suggest that intra-hippocampal beta A1-40 administration alters cholinergic transmission, but these alterations may be mild and thus do not lead to obvious working memory deficits in a DMTP task in well-trained animals.

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline.