5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore.

BACKGROUND: Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. METHODS: A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. RESULTS: Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke patients. CONCLUSIONS: Five year post-stroke survival and rehospitalization due to stroke recurrence as well as their associations with patient demographics were studied for different stroke types in Singapore. Specific preventive strategies are needed to target the high risk groups to improve their long-term outcomes after acute stroke.

Low and moderate doses of acute ethanol do not impair spatial cognition but facilitate accelerating rotarod performance in adolescent and adult rats.

Adolescents and adult rodents have differing sensitivities to the acute effects of ethanol on a variety of behavioral and electrophysiological measures. Often, these differences are revealed using high ethanol doses and consequently little is known about these age-related effects using lower ethanol doses. We sought to determine if low-dose ethanol produces differential effects on cognition and motor behavior in adolescent and adult rats. Adolescent (postnatal day PD 30-32) and adult (PD 70-72) male Sprague Dawley rats were trained on the standard version of the Morris Water Maze (MWM) for 5 days or received 5 training trials on an accelerating rotarod (ARR). Adolescents learned the location of the submerged platform in the MWM significantly slower than adults during training and, acute ethanol administration (0.5 g/kg, 0.75 g/kg, or 1.0 g/kg) 30 min before testing did not impair spatial memory in either age group. On the ARR test, adolescent rats spent significantly more time on the rotarod compared to adults and, alcohol exposure (1.0 g/kg) significantly increased ARR performance 30 min following administration. Our findings address the utility of investigating low and moderate doses of ethanol during different developmental stages in rats.

Effect of acute ethanol and acute allopregnanolone on spatial memory in adolescent and adult rats.

The effects of ethanol differ in adolescent and adult rats on a number of measures. The evidence of the effects of ethanol on spatial memory in adolescents and adults is equivocal. Whether adolescents are more or less sensitive to ethanol-induced impairment of spatial memory acquisition remains unclear; with regard to the effects of acute ethanol on spatial memory retrieval there is almost no research looking into any age difference. Thus, we examined the effects of acute ethanol on spatial memory in the Morris Watermaze in adolescents and adults. Allopregnanolone (ALLO) is a modulator of the GABA(A) receptor and has similar behavioral effects as ethanol. We sought to also determine the effects of allopreganolone on spatial memory in adolescent and adults. Male adolescent (post natal [PN]28-30) and adult (PN70-72) rats were trained in the Morris Watermaze for 6 days and acute doses of ethanol (saline, 1.5 and 2.0 g/kg) or ALLO (vehicle, 9 and 18 mg/kg) were administered on Day 7. A probe trial followed on Day 8. As expected, there were dose effects; higher doses of both ethanol and ALLO impaired spatial memory. However, in both the ethanol and ALLO conditions adolescents and adults had similar spatial memory impairments. The current results suggest that ethanol and ALLO both impair hippocampal-dependent spatial memory regardless of age in that once learning has occurred, ethanol or ALLO does not differentially impair the retrieval of spatial memory in adolescents and adults. Given the mixed results on the effect of ethanol on cognition in adolescent rats, additional research is needed to ascertain the factors critical for the reported differential results.

Behavioral effects of ethanol in cerebellum are age dependent: potential system and molecular mechanisms.

BACKGROUND: Adolescent rats are less sensitive to the motor-impairing effects of ethanol than adults. However, the cellular and molecular mechanisms underlying this age-dependent effect of ethanol have yet to be fully elucidated. METHOD: Male rats of various ages were used to investigate ethanol-induced ataxia and its underlying cellular correlates. In addition, Purkinje neurons from adolescent and adult rats were recorded both in vivo and in vitro. Finally, protein kinase C (PKCγ) expression was determined in 3 brain regions in both adolescent and adult rats. RESULTS: The present multi-methodological investigation confirms that adolescents are less sensitive to the motor-impairing effects of ethanol, and this differential effect is not because of differential blood ethanol levels. In addition, we identify a particular cellular correlate that may underlie the reduced motor impairment. Specifically, the in vivo firing rate of cerebellar Purkinje neurons recorded from adolescent rats was insensitive to an acute ethanol challenge, while the firing rate of adult cerebellar Purkinje neurons was significantly depressed. Finally, it is demonstrated that PKCγ expression in the cortex and cerebellum mirrors the age-dependent effect of ethanol: adolescents have significantly less PKCγ expression compared to adults. CONCLUSIONS: Adolescents are less sensitive than adults to the motor-impairing effects of ethanol, and a similar effect is seen with in vivo electrophysiological recordings of cerebellar Purkinje neurons. While still under investigation, PKCγ expression mirrors the age effect of ethanol and may contribute to the age-dependent differences in the ataxic effects of ethanol.

Effects of ethanol on hippocampal function during adolescence: a look at the past and thoughts on the future.

It has been demonstrated by several laboratories that ethanol, both acute and chronic, produces effects that are age dependent. Specifically, adolescent rats are less sensitive to the hypnotic and motor-impairing effects of ethanol but are more sensitive to the hypothermic effects of the drug. However, the results on hippocampal function are not as clear. For example, there have been mixed findings regarding adolescent sensitivity of hippocampal-dependent (spatial) memory in response to ethanol. The current review explores the present state of the field as it relates to ethanol's effects in the hippocampus, particularly as it relates to spatial memory. In addition, we review potential neurobiological mechanisms that might underlie the age-dependent effects of ethanol in the hippocampus. Finally, future directions are proposed that will advance the state of the field as it relates to ethanol's effect during this developmental period.