Effect of COVID-19 on Emergent Stroke Care: A Regional Experience.

BACKGROUND AND PURPOSE: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. METHODS: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. RESULTS: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%-46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%-51%), and specifically thrombolysis by 33% (95% CI, 4%-55%), but this finding had less precision. CONCLUSIONS: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.

Risk of intracerebral haemorrhage from hypertension is greatest at an early age.

INTRODUCTION: The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. PATIENTS AND METHODS: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. RESULTS: Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). DISCUSSION: Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.

Cell proliferation and survival in the mating circuit of adult male hamsters: effects of testosterone and sexual behavior.

The transient actions of gonadal steroids on the adult brain facilitate social behaviors, including reproduction. In male rodents, testosterone acts in the posterior medial amygdala (MeP) and medial preoptic area (MPOA) to promote mating. Adult neurogenesis occurs in both regions. The current study determined if testosterone and/or sexual behavior promote cell proliferation and survival in MeP and MPOA. Two experiments were conducted using the thymidine analog BrdU. First, gonad-intact and castrated male hamsters (n=6/group) were compared 24 h or 7 weeks after BrdU. In MeP, testosterone-stimulated cell proliferation 24 h after BrdU (intact: 22.8+/-3.9 cells/mm(2), castrate: 13.2+/-1.4 cells/mm(2)). Testosterone did not promote cell proliferation in MPOA. Seven weeks after BrdU, cell survival was sparse in both regions (MeP: 2.5+/-0.6 and MPOA: 1.7+/-0.2 cells/mm(2)), and was not enhanced by testosterone. In Experiment 2, gonad-intact sexually-experienced animals were mated weekly to determine if regular neural activation enhances cell survival 7 weeks after BrdU in MeP and MPOA. Weekly mating failed to increase cell survival in MeP (8.1+/-1.6 vs. 9.9+/-3.2 cells/mm(2)) or MPOA (3.9+/-0.7 vs. 3.4+/-0.3 cells/mm(2)). Furthermore, mating at the time of BrdU injection did not stimulate cell proliferation in MeP (8.9+/-1.7 vs. 8.1+/-1.6 cells/mm(2)) or MPOA (3.6+/-0.5 vs. 3.9+/-0.7 cells/mm(2)). Taken together, our results demonstrate a limited capacity for neurogenesis in the mating circuitry. Specifically, cell proliferation in MeP and MPOA are differentially influenced by testosterone, and the birth and survival of new cells in either region are not enhanced by reproductive activity.

Testosterone as a discriminative stimulus in male rats.

Testosterone and other anabolic-androgenic steroids (AAS) are reinforcing in animals, as determined by conditioned place preference or self-administration. Most drugs of abuse produce subjective effects on mood and perception that initiate and maintain drug taking. Whether AAS have similar effects is not known. Food-restricted male Sprague-Dawley rats (n=9) were tested for their ability to discriminate an injection of testosterone from the ß-cyclodextrin vehicle using a standard two-lever operant paradigm. In drug discrimination, animals use the subjective effects of drug or vehicle to select the appropriate lever to obtain food pellets under an FR10 schedule of reinforcement. All rats demonstrated vigorous responding for food (1415.1±76.1 responses/20 min) with 94.9% of responses on the active lever. For the first 30 days, rats received 1mg/kg testosterone sc 30 min before testing. On Day 14, one rat achieved the discrimination criteria of 9/10 consecutive days with >90% responses on the active lever and ≤5 responses on the inactive lever before the first reinforcement. Subsequently, rats were tested with testosterone at different doses (2, 7.5, 15 mg/kg at 30 min before testing) and times (2mg/kg at 30 or 60 min before testing), each for 20 days. One additional rat demonstrated successful discrimination at Day 54 with 2mg/kg testosterone 60 min before testing. The remaining 7 rats failed to discriminate testosterone within 110 days. When analyzed according to less-stringent standards, 4 additional rats met criteria for testosterone discrimination. However, continued performance was not stable. Thus, testosterone was unable to consistently support drug discrimination. We conclude that testosterone does not produce rapid interoceptive effects (NIH DA12843 to RIW).

MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse.

Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4 × 20 mg/kg) or saline (n = 11-12/group). The right striatum was immunostained for tyrosine hydroxylase (TH). The left hemisphere was stained by Golgi Cox to quantify neuronal morphology in medium spiny neurons (MSNs) of the dorsolateral striatum. MPTP reduced TH, but there was no effect of castration and no interaction. For MSN dendritic morphology, MPTP decreased the highest branch order and increased spine density on 2nd-order dendrites. Castrated males had shorter 5th-order dendrites. However, there was no interaction between gonadal status and MPTP. Thus, castration and MPTP exert nonoverlapping effects on MSN morphology with castration acting on distal dendrites and MPTP acting proximally.

Sex differences in motor behavior in the MPTP mouse model of Parkinson's disease.

Sex differences in Parkinson's disease (PD) have been reported in humans and rodent models, with a higher incidence in men and increased severity in male rodents. The current study examined sex differences and the effects of gonadal steroid hormones in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of PD. Male (n=51) and female (n=50) mice were gonadectomized and received physiologic replacement with testosterone or estrogen (Experiment 1), or no hormones (Experiment 2). Two weeks later, mice received either MPTP (10 mg/kg per day for 5 days) or saline. Higher doses killed female mice. Mice were tested one week after MPTP for motor performance using rotarod, pole and gait tests. In hormone-treated mice, males significantly outperformed females in all three tests (p<0.05). Compared with females, males had a greater overall rotarod performance (ORP: 1317.1+/-98.3 vs. 988.1+/-95.6), descended a pole faster (7.1+/-0.6 vs. 9.6+/-0.7s), and had longer stride lengths (hindlimb 7.3+/-0.1 vs. 6.8+/-0.1cm). By contrast, ovariectomized female mice receiving saline outperformed castrated males on the rotarod (1296.6+/-83.3 vs. 811.2+/-113.7, p<0.05) and descended a pole faster (9.7+/-2.0 vs. 15.6+/-1.9s, p<0.05). MPTP significantly impaired ORP (p<0.05) in hormone-treated males (703.7+/-65.5) and females (432.8+/-88.6, p<0.05). After MPTP, stride length was selectively decreased in males (hindlimb 6.6+/-0.1 cm, p<0.05), and pole test performance was unimpaired in either sex. After gonadectomy, MPTP did not decrease motor performance in males (p>0.05) but significantly reduced ORP in females (975.9+/-110.3 vs. saline females, p<0.05). Our results show that small, chronic doses of MPTP produce subtle, sexually-dimorphic impairments in motor performance, but without a loss of tyrosine hydroxylase-positive neurons in the substantia nigra. In gonadectomized mice, this sex difference is reversed.