Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by nonspecific symptomatology (eg, headache, visual disturbances, encephalopathy, and seizures) and classically cortical and subcortical vasogenic edema predominantly affecting the parietooccipital region. PRES etiologies are usually dichotomized into toxic PRES (eg, antineoplastic drugs, illicit drugs) and clinical condition-associated PRES (eg, acute hypertension, dysimmune disorders). Although the pathophysiology of PRES remains elusive, 2 main pathogenic hypotheses have been suggested: cerebral hyperperfusion due to acute hypertension and cerebral hypoperfusion related to endothelial dysfunction. Research into the pathogenesis of PRES has emerged through the development of animal models in the last decade. The motivation for developing a suitable PRES model is 2-fold: to fill in knowledge gaps of the pathophysiological mechanisms involved, and to open new perspectives for clinical assessment of pharmacological targets to improve therapeutic management of PRES. All current models of PRES have a hypertensive background, on which other triggers (acute hypertension, inflammatory, drug toxicity) have been added to address specific facets of PRES (eg, seizures). The initial model consisted in inducing a reduced uterine perfusion pressure that mimics preeclampsia, a leading cause of PRES. More recently, a model of stroke-prone spontaneously hypertensive rats on high-salt diet, originally developed for hypertensive small vessel disease and vascular cognitive impairment, has been studied in PRES. This review aims to discuss, depending on the research objective, the benefits and limitations of current experimental approaches and thus to define the desirable characteristics for studying the pathophysiology of PRES and developing new therapies.

Curcumin has protective actions in neuropsychiatric disorders, acting as a neuroprotective agent. As a first approach, the study aimed at a systematic review of the potential effects of curcumin on cognitive performance for attention-deficit-hyperactivity disorder (ADHD). This research was carried out in the databases of PubMed, Embase, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and the Grey literature. Upon discovering the scarcity of relevant studies, and knowing that curcumin might have an ADHD hyperactive and anxious behavior, the study proposed to evaluate the effects of curcumin in an ADHD phenotype of spontaneously hypertensive Wistar rats (SHR). No studies were found that related to curcumin and ADHD. Fifteen SHRs were then divided into separate groups that received water (1 mg/kg/day), curcumin (50 mg/kg/day), or methylphenidate (1 mg/kg/day) for 42 days. Behavioral tests to assess activity (Open Field Test), anxiety and impulsivity (Elevated Plus-Maze, and Social Interaction), and memory (Y-Maze, and the Object Recognition Test) were all performed. The animals that were treated with curcumin showed less anxious and hyperactive behavior, as seen in the Open Field Test and the Social Interaction Test. Anxious behavior was measured by the EPM and was not modulated by any treatment. The results of the Y-Maze Test demonstrated that curcumin improved spatial memory. In the Object Recognition Test, neither the short nor the long-term memory was improved. The treatments that were used in this study beneficially modulated the anxious and hyperactive behavior of the SHR.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition related to several negative outcomes, and its pathophysiology is still poorly understood. The spontaneously hypertensive rats (SHRs) are the most commonly used animal model of ADHD. How ever, its validity, and especially its predictive validity, has been questioned. Therefore, the current protocol discloses the background, aims and methods of a systematic review and meta-analysis of studies reporting the behavioural effects of methylphenidate (MPH), the most commonly prescribed treatment for ADHD, in the SHR.
METHODS: Studies will be identified through a literature search using three different electronic databases: Medline, Embase and Web of Science. There will be no language restrictions. All s tudies that administered MPH to SHR and evaluated locomotion, attention, impulsivity or memory will be included.
UNASSIGNED: Studies will be prescreened based on title and abstract, and a full-text review will be performed if necessary. Screening will be performed by two authors, and any disagreement will be discussed with a third author.
UNASSIGNED: Data extraction will be performed by two independent authors according to a standardised form. Studies will be grouped according to the behavioural outcomes reported, and a meta-analysis will be performed for each group. The influence of predefined covariates on the effects of MPH will be evaluated using meta-regression and sensitivity analyses. Data will be reported following PRISMA guidelines.

Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.

The spontaneously hypertensive rats (SHR) are the most widely used model for ADHD. While face and construct validity are consolidated, questions remain about the predictive validity of the SHR model. We aim at summarizing the evidence for the predictive validity of SHR by evaluating its ability to respond to methylphenidate (MPH), the most well documented treatment for ADHD. A systematic review was carried out to identify studies evaluating MPH effects on SHR behavior. Studies (n=36) were grouped into locomotion, attention, impulsivity or memory, and a meta-analysis was performed. Meta-regression, sensitivity, heterogeneity, and publication bias analyses were also conducted. MPH increased attentional and mnemonic performances in the SHR model and decreased impulsivity in a dose-dependent manner. However, MPH did not reduce hyperactivity in low and medium doses, while increased locomotor activity in high doses. Thus, since the paradoxical effect of stimulant in reducing hyperactivity was not observed in the SHR model, our study does not fully support the predictive validity of SHR, questioning their validity as an animal model for ADHD.

We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR), and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001-2010), and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress.

The spontaneously hypertensive stroke prone rat is best known as an inducible model of large artery stroke. Spontaneous strokes and stroke propensity in the spontaneously hypertensive stroke prone rat are less well characterized; however, could be relevant to human lacunar stroke. We systematically reviewed the literature to assess the brain tissue and small vessel pathology underlying the spontaneous strokes of the spontaneously hypertensive stroke prone rat. We searched systematically three online databases from 1970 to May 2010; excluded duplicates, reviews, and articles describing the consequences of induced middle cerebral artery occlusion or noncerebral pathology; and recorded data describing brain region and the vessels examined, number of animals, age, dietary salt intake, vascular and tissue abnormalities. Among 102 relevant studies, animals sacrificed after developing stroke-like symptoms displayed arteriolar wall thickening, subcortical lesions, enlarged perivascular spaces and cortical infarcts and hemorrhages. Histopathology, proteomics and imaging studies suggested that the changes not due simply to hypertension. There may be susceptibility to endothelial permeability increase that precedes arteriolar wall thickening, degeneration and perivascular tissue changes; systemic inflammation may also precede cerebrovascular changes. There were very few data on venules or tissue changes before hypertension. The spontaneously hypertensive stroke prone rat shows similar features to human lacunar stroke and may be a good spontaneous model of this complex human disorder. Further studies should focus on structural changes at early ages and genetics to identify factors that predispose to vascular and brain damage.

Over the last decade, adenosine receptors in the central nervous system have been implicated in the modulation of cognitive functions. Despite the general view that endogenous adenosine modulates cognition through the activation of adenosine A1 receptors, evidence is now emerging on a possible role of A2A receptors in learning and memory. The present review attempts to examine results reported in different studies using diverse animal models, to provide a comprehensive picture of the recent evidence of a relationship between adenosinergic function and memory deficits. The present data suggest that caffeine (a nonselective adenosine receptor antagonist) and selective adenosine A2A receptor antagonists can improve memory performance in rodents evaluated through different tasks. They might also afford protection against memory dysfunction elicited in experimental models of aging, Alzheimer\'s disease, Parkinson\'s disease and, in spontaneously hypertensive rats (SHR), a putative genetic model of attention deficit hyperactivity disorder (ADHD).

Nitric oxide (NO) is an important gas molecule that plays a pivotal role in physiology and pathology in various systems. Our laboratory has been working on the hypertensive cardiovascular disorders and pulmonary edema for more than 30 years. In this brief review article, we have described the role of NO in hypertension, pulmonary disorders, sepsis, and to some extent, the endothelial factors on the arterial baroreceptors and cerebral blood flow. Our studies indicate that the vasodilatory effects of endogenous NO act primarily on the small resistance vessels. The large conduit vessels are less affected. In contrast to the earlier work suggesting that NO or endothelial function is impaired in hypertension, we have provided evidence to indicate that the NO release or function is enhanced in rats with hypertension. Chronic NO deprivation in rats with spontaneous hypertension facilitates the progression of hypertension to malignant phase with marked functional and structural changes in blood vessels of various organs. In most studies using isolated perfused lungs, our results show that NO exerts toxic effect on the lung injury following ischemia/reperfusion, air embolism, endotoxemia and hypoxia. Recent clinical investigations have revealed that the inducible NO synthase (iNOS) expression was increased in patients with enterovirus and other infections, suggesting a detrimental role of iNOS and NO in the acute lung injury. In this review article, we have also provided the experiences, results and stories in our laboratory during a relatively long period investigating the good and bad sides of NO on the cardiopulmonary functions. The purposes are two-fold: first, to share the experience and stories for scientific and educational purposes; and second, to encourage young investigators to continue work on many questions yet unanswered.

OBJECTIVE: There is a need for practical and sensitive preclinical tests for detecting the kidney toxicity of chemicals. The spontaneously hypertensive rat (SHR), as it ages, develops renal and cardiovascular changes similar to those considered as human risk factors for radiocontrast-induced renal damage. Age, male gender, and uncontrolled hypertension make these animals susceptible to the volume and osmolality of the administered contrast agent and the effect of repeated contrast administration after a brief interval. This article reviews studies in which the role of these and other factors were evaluated to validate the male SHR as a small animal model for renal damage induced by contrast and other agents.
METHODS: Systolic blood pressure was measured with a tail cuff before and after the administration of the experimental substances, and the left kidney and heart were studied histologically to determine the influence of age, dose of contrast repeated at a short interval, gender and strain, the role of the sympathetic adrenergic nervous system, osmolality, and apoptosis.
RESULTS: As the animals aged and the systolic blood pressure remained elevated, the animals developed progressive renal lesions that worsened after the administration of contrast. The most advanced renal lesions occurred in adult male SHRs that received two doses of contrast 6 hours apart. Female SHR rats and male Wistar Kyoto rats showed no effect or only minimal changes in heart and kidneys after the administration of contrast compared with age-matched male SHRs. Adrenergic blockade allowed only a small elevation in systolic blood pressure after contrast administration but did not protect the kidneys against renal damage by contrast. Hypaque, Omnipaque, and mannitol caused renal damage in proportion to their osmolality. Apoptosis with Hypaque, Omnipaque, and mannitol was observed in the kidney and heart.
CONCLUSIONS: The results indicate that the aging male SHR develops spontaneous renal lesions that progress with age, increasing the susceptibility to the renal-damaging effects of contrast. Thus, the aging male SHR provides a laboratory tool for detecting the risk of renal damage of new contrast media as well as other pharmaceuticals and assessing methods to protect the kidneys and possible mechanisms of renal damage.