American Indian and Alaska Native veterans in the Indian Health Service: Health status, utilization, and cost.

PURPOSE: Many rural American Indian and Alaska Native (AIAN) veterans receive care from the Indian Health Service (IHS). United States Department of Veterans Affairs (VA) has reimbursement agreements with some IHS facilities and tribal programs and seeks to expand community partnerships in tribal areas, but details of how AIAN veterans use IHS are unknown. We aimed to assess the health status, service utilization patterns, and cost of care of veterans who use IHS. METHODS: We used comprehensive and integrated IHS data to compare health status, health service utilization and treatment cost of veterans (n = 12,242) to a matched sample of non-veterans (n = 12,242). We employed logistic, linear, or negative binomial regressions as appropriate, by sex and overall. FINDINGS: Compared to non-veterans, veterans had lower odds of having hypertension, renal disease, all-cause dementia, and alcohol or drug use disorders, but had similar burden of other conditions. In service utilization, veterans had lower hospital inpatient days; patterns were mixed across outpatient services. Unadjusted treatment costs for veterans and non-veterans were $3,923 and $4,145, respectively; veteran adjusted treatment costs were statistically lower. Differences in significance by sex were found for health conditions and service use. CONCLUSIONS: AIAN veterans, compared to AIAN non-veterans, were not less healthy, nor did they require more intensive or more costly care under IHS. Our results indicate the viability and importance of expanding IHS-VA partnerships in community care.

Suicide Among American Indian and Alaska Native Veterans Who Use Veterans Health Administration Care: 2004-2018.

BACKGROUND: American Indian and Alaska Natives (AI/ANs) veterans may be at elevated risk for suicide, but little is known about suicide among this population. METHODS: We conducted a retrospective cohort analysis of AI/AN veterans who received health care services provided or paid for by the Veterans Health Administration (VHA) between October 1, 2002, and September 30, 2014, and who were alive as of September 30, 2003. Age-specific and age-adjusted suicide rates through 2018, per 100,000 person-years (PY) at risk and 95% confidence intervals were computed. RESULTS: Age-adjusted suicide rates among AI/AN veterans in this cohort more than doubled (19.1-47.0/100,000 PY) over the 15-year observation period. In the most recent observation period (2014-2018), the age-adjusted suicide rate was 47.0 per 100,000 PY, with the youngest age group (18-39) exhibiting the highest suicide rate (66.0/100,000 PY). The most frequently used lethal means was firearms (58.8%), followed by suffocation (19.3%), poisoning (17.2%), and other (4.7%). CONCLUSIONS: Results suggest that: (1) suicide is an increasing problem among AI/AN VHA veterans; and (2) younger AI/AN VHA veterans are at particularly high risk and warrant focused prevention efforts. Findings are similar to those observed in general AI/AN population. There is a compelling need to review and strengthen VHA suicide prevention efforts directed towards AI/AN veterans.

A scoping review of veteran suicide prevention programs in Native American communities and in the general population.

Suicide is a major public health problem that disproportionately impacts veterans in the general U.S. population. Recent analyses indicate that American Indian and Alaska Native (AI/AN) veterans may be two to three times as likely as non-Hispanic White veterans to experience suicidal ideation. Although suicide prevention programs have been successfully implemented for many at-risk populations, to our knowledge, none have been designed or implemented for AI/AN veterans. To address this gap, we conducted a scoping review of suicide prevention programs with the objective of identifying promising strategies and lessons learned to identify promising practices for preventing suicide among AI/AN veterans. We conducted two parallel literature searches-a review of suicide prevention programs for the general U.S. adult population and AI/AN communities. We rated programs on 16 criteria, covering five domains-best practices in suicide prevention, U.S. Department of Veterans Affairs (VA) Office of Rural Health Promising Practice criteria, cultural fit, care coordination, and outcomes. Our findings indicate that many of the VA evidence-based or best practice programs are available system-wide, but none have been tailored for AI/AN veterans or the communities in which they live. Conversely, we found that many culturally specific programs implemented in AI/AN communities were rarely disseminated beyond tribal land and none were specifically developed for veterans. Based upon these findings, and to advance suicide prevention programs for AI/AN veterans, we propose a suicide prevention model that builds upon existing VA infrastructure to disseminate best practices to AI/AN communities and integrate tribal-specific cultural approaches to suicide prevention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Suicide-related behaviors among American Indian and Alaska Native Veterans: A population-based analysis.

American Indian and Alaska Native (AI/AN) Veterans are at elevated risk for suicide, but currently, no population-based research exists on precursors, including ideation, plans, or attempts. We employed two large national surveys to investigate the occurrence of suicide-related behaviors among AI/AN Veterans. Using cross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS, 2010-2012) and National Survey on Drug Use and Health (NSDUH, 2010-2015), we compared weighted frequencies of suicide ideation in AI/AN Veterans and non-Hispanic White (NHW) Veterans. Suicide ideation among AI/AN Veterans was 9.1% (95%CI = 3.6%, 21.5%) and 8.9% (95%CI = 1.9%, 15.9%) in BRFSS and NSDUH, respectively, compared to 3.5% (95%CI = 3.0%, 4.1%) and 3.7% (95%CI = 3.0%, 4.4%) for NHW Veterans. Logit analysis suggested higher odds of ideation among AI/AN Veterans in both samples (NDSUH: OR = 2.68, 95%CI = 1.14-6.31; BRFSS: OR = 2.66, 95% CI 0.96-7.38), although sample sizes were small and confidence intervals were wide. Consistent findings from two national samples suggest AI/AN Veterans have more than twice the risk of suicide ideation relative to NHW Veterans. Ongoing efforts include weighing these results together with data on suicide deaths from medical and death records to develop effective suicide prevention approaches in collaboration with AI/AN Veterans and their communities.

Older Adults' Perceptions of a Church-Based Social Marketing Initiative to Prevent Falls Through Balance and Strength Classes.

Despite evidence that balance and strength training and other multicomponent exercise classes reduce the risk and rate of falls and fall-related injuries, few older adults participate. To increase uptake of balance- and strength-based fall-prevention classes, we designed and implemented a social marketing program, delivered through churches. Diverse stakeholders in this social marketing initiative included class participants, instructors, church leaders and members, and public health and recreation partners. We used interpretive description to explore perceptions of the social marketing messages and the barriers and facilitators older church members encountered to balance-class enrollment and adherence. The results were three practical, clinically relevant thematic summaries of older adults' experience. The marketing initiative succeeded in helping older adults hear about the classes, decide whether classes fit their lifestyle and needs, and continue attendance.

Factors Associated With Older Adults' Enrollment in Balance Classes to Prevent Falls: Case-Control Study.

Balance training decreases fall risk among older adults, but few participate in such training. We examined the association of exposure to social marketing to promote balance classes, personal characteristics and other factors, with older adults' balance class participation. Adults aged ⩾60 years were eligible for this case-control study if they attended any church enrolled in a trial testing the effect of social marketing on balance class participation. Cases attended balance classes during the study period; controls were randomly sampled congregants who did not join a class. Cases were more likely to attend churches that received the social marketing program, and were older, more often female, and more frequently experienced "near falls" than controls. Participation was also associated with increasing age of the church's leader and rural church attendance. Programs to promote balance classes may need to be tailored to target some risk groups, including men and urban and suburban congregants.

Outcomes and Lessons Learned from the Tribal Veterans Representative Program: A Model for System Engagement.

American Indian and Alaska Native Veterans are more rural than Veterans of any other race or ethnicity and face significant barriers to accessing care. Since 2001, the Tribal Veterans Representative (TVR) Program, a partnership between the U.S. Department of Veterans Affairs (VA) and tribal nations, has trained liaisons from tribal communities to facilitate access to VA benefits and services. We delineate the TVR program model alongside supporting data. We reviewed TVR training materials and program evaluations to identify components of the program essential for increasing access to VA services and benefits. We then report a quantitative assessment of benefits attained in one tribal community. The TVR model is characterized by the exchange of two sets of knowledge and resources-'institutional' and 'community'-during a co-sponsored educational program aiming to train community liaisons about the institution. The institution leads the program's content; the community's traditions inform its process. Following the program, liaisons use support networks comprising trainers, trainees and local organizations to teach other community members to access health care and benefits. In the evaluation community, one liaison has facilitated access for hundreds of Veterans, with financial compensation exceeding $400,000 annually. The TVR program has begun to demonstrate its utility for other rural populations, though further formal evaluation is recommended. Compared with similar models to increase rural populations' access to health care and benefits, the long-term support networks from the TVR model may be most useful when the institution must build trust and engage with the target population.

Methodology for Evaluating Models of Telemental Health Delivery Against Population and Healthcare System Needs: Application to Telemental Healthcare for Rural Native Veterans.

Background: Rural American Indian and Alaska Native (AI/AN) Veterans face exceptional barriers to receiving quality mental healthcare. We aimed to identify models of in-person and telemental health service delivery with promise for adaptation and wide dissemination to rural AI/AN Veterans. Methods: Our method for matching specific populations with models of care includes (1) selecting frameworks that represent the healthcare organization's goals, (2) identifying relevant service delivery models for the target population(s), (3) assessing models against the selected frameworks, and (4) summarizing findings across models. We applied this approach to rural AI/AN Veteran populations. Results: Searches identified 13 current models of service delivery for rural AI/AN Veteran, rural AI/AN, and general rural Veteran populations. These models were assessed against four frameworks-the U.S. Department of Veterans Affairs' Office of Rural Health's Promising Practices, Veterans Health Administration's Guide to Mental Health Services, the Institute for Healthcare Improvement's Triple Aim Framework, and the American Indian Telemental Health Clinic framework. Discussion: The one model used for service delivery for rural AI/AN Veterans increases access and is patient-centered but lacks operational feasibility. Models for rural AI/ANs also increase access and are patient-centered but generally lack effectiveness evaluations. Models for rural Veterans demonstrate beneficial effects on mental health outcomes but do not emphasize cultural adaptations to diverse populations. Conclusions: Our approach to selecting models of service delivery considers the needs of operational partners as well as target populations and emphasizes large-scale implementation alongside effectiveness. Pending further testing, this approach holds promise for wider application.

Rural American Indian and Alaska Native veterans' telemental health: A model of culturally centered care.

American Indian and Alaska Native (AI/AN) veterans living in rural areas have unique health care needs and face numerous barriers to accessing health care services. Among these needs is a disproportionate prevalence of posttraumatic stress disorder and other mental illnesses. Since 2001, 14 rural communities have partnered with the U.S. Department of Veterans Affairs and the Centers for American Indian and Alaska Native Health at the University of Colorado Anschutz Medical Campus to extend telemental health clinics to American Indian veterans. Administrative and, to some extent, clinical considerations of these clinics have been reviewed previously. This paper describes a model of care, evolved over a 14-year period, that weaves together evidence-based Western treatment, traditional Native healing, and rural Native communities into 4 main components: mental health care, technology, care coordination, and cultural facilitation. We delineate improvements to care made by addressing barriers such as system transference, provider-patient trust, and videoconferencing. Similarly, the discussion notes ways that the care model leverages strengths within Native communities, such as social cohesion and spirituality. Future steps include selection of appropriate performance indicators for systematic evaluation. The identification of key constructs of this care model will facilitate comparisons with other models of care in underserved populations with chronic and complex health conditions, and eventually advance the state of care for our warriors. (PsycINFO Database Record

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

BACKGROUND: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. OBJECTIVE: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. METHODS: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. RESULTS: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. CONCLUSIONS: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.

Interventions for primary prevention of suicide in university and other post-secondary educational settings.

BACKGROUND: Suicide is a leading cause of death among post-secondary students worldwide. Suicidal thoughts and planning are common among post-secondary students. Previous reviews have examined the effectiveness of interventions for symptomatic individuals; however, many students at high risk of suicide are undiagnosed and untreated. OBJECTIVES: We evaluated the effect on suicide and suicide-related outcomes of primary suicide prevention interventions that targeted students within the post-secondary setting. SEARCH METHODS: We searched the following sources up to June 2011: Specialised Registers of two Cochrane Groups, Cochrane Central Register of Controlled Trials, and nine other databases, trial registers, conference proceedings, and websites of national and international organizations. We screened reference lists and contacted authors of included studies to identify additional studies. We updated the search in November 2013; we will include these results in the review's next update. SELECTION CRITERIA: We included studies that tested an intervention for the primary prevention of suicide using a randomized controlled trial (RCT), controlled before-and-after (CBA), controlled interrupted time series (CITS), or interrupted time series (ITS) study design. Interventions targeted students within the post-secondary setting (i.e. college, university, academy, vocational, or any other post-secondary educational institution) without known mental illness, previous suicide attempt or self-harm, or suicidal ideation. Outcomes included suicides, suicide attempts, suicidal ideation, changes in suicide-related knowledge, attitudes and behavior, and availability of means of suicide. DATA COLLECTION AND ANALYSIS: We used standardized electronic forms for data extraction, risk of bias and quality of evidence determination, and analysis. We estimated standardised mean differences (SMD) with 95% confidence intervals (CIs). We analysed studies by intervention type and study design. We summarized RCT effect sizes using random-effects models meta-analyses; and analysed statistical heterogeneity using the Chi(2) test and I(2) statistic. We described narratively the results from studies that used other study designs. MAIN RESULTS: Eight studies met inclusion criteria. They were heterogeneous in terms of participants, study designs, and interventions. Five of eight studies had high risk of bias. In 3 RCTs (312 participants), classroom-based didactic and experiential programs increased short-term knowledge of suicide (SMD = 1.51, 95% CI 0.57 to 2.45; moderate quality evidence) and knowledge of suicide prevention (SMD = 0.72, 95% CI 0.36 to 1.07; moderate quality evidence). The effect on suicide prevention self-efficacy in one RCT (152 participants) was uncertain (SMD = 0.20, 95% CI -0.13 to 0.54; low quality evidence). One CBA analysed the effects of an institutional policy that restricted student access to laboratory cyanide and mandated professional assessment for suicidal students. The incidence of student suicide decreased significantly at one university with the policy relative to 11 control universities, 2.00 vs. 8.68 per 100,000 (Z = 5.90; P < 0.05). Four CBAs explored effects of training 'gatekeepers' to recognize and respond to warning signs of emotional crises and suicide risk in students they encountered. The magnitude of effect sizes varied between studies. Gatekeeper training enhanced short-term suicide knowledge in students, peer advisors residing in student accommodation, and faculty and staff, and suicide prevention self-efficacy among peer advisors. There was no evidence of an effect on participants' suicide-related attitudes or behaviors. One CBA found no evidence of effects of gatekeeper training of peer advisors on suicide-related knowledge, self-efficacy, or gatekeeper behaviors measured four to six months after intervention. AUTHORS' CONCLUSIONS: We found insufficient evidence to support widespread implementation of any programs or policies for primary suicide prevention in post-secondary educational settings. As all evaluated interventions combined primary and secondary prevention components, we were unable to determine the independent effects of primary preventive interventions. Classroom instruction and gatekeeper training increased short-term suicide-related knowledge. We found no studies that tested the effects of classroom instruction on suicidal behavior or long-term outcomes. Limited evidence suggested minimal longer-term effects of gatekeeper training on suicide-related knowledge, while no evidence was found evaluating its effect on suicidal behavior. A policy-based suicide intervention reduced student suicide, but findings have not been replicated. Our findings are limited by the overall low quality of the evidence and the lack of studies from middle- and low-income countries. Rigorously designed studies should test the effects of preventive interventions on important health outcomes, including suicidal ideation and behavior, in varying post-secondary settings.

Church-based social marketing to motivate older adults to take balance classes for fall prevention: cluster randomized controlled trial.

OBJECTIVE: Determine whether a church-based social marketing program increases older adults' participation in balance classes for fall prevention. METHODS: In 2009-10, 51 churches (7101 total members aged ≥ 60) in Colorado, U.S.A. were randomized to receive no intervention or a social marketing program. The program highlighted benefits of class participation (staying independent, building relationships), reduced potential barriers (providing convenient, subsidized classes), and communicated marketing messages through church leaders, trained "messengers," printed materials and church-based communication channels. Between-group differences in balance class enrollment and marketing message recall among congregants were compared using Wilcoxon Two-Sample Test and regression models. RESULTS: Compared to 25 control churches, 26 churches receiving the social marketing program had a higher median proportion (9.8% vs. 0.3%; p<0.001) and mean number (7.0 vs. 0.5; IRR=11.2 [95%CI: 7.5, 16.8]) of older adult congregants who joined balance classes. Intervention church members were also more likely to recall information about preventing falls with balance classes (AOR=6.2; 95% CI: 2.6, 14.8) and availability of classes locally (AOR=7.7; 95% CI: 2.6, 22.9). CONCLUSIONS: Church-based social marketing effectively disseminated messages about preventing falls through balance classes and, by emphasizing benefits and reducing barriers and costs of participation, successfully motivated older adults to enroll in the classes.

Understanding fall meaning and context in marketing balance classes to older adults.

This study explored older, community-dwelling adults' attitudes and values about proposed church-delivered balance classes for fall prevention. Community observation, group interviews with stakeholders, key informant interviews, and focus groups with church members ≥ 60 years of age were analyzed in two ways: first for inductive themes expressing community sentiment about fall prevention for older adults, then for content useful in creating locally tailored social marketing messages. Four themes expressed perceptions of fall-prevention programming: de-emphasizing fall risk and emphasizing strength and independence, moving older adults out of their "comfort zones" to join classes, identifying relationships to support fall-prevention activities, and considering gender-based differences in approaches to fall prevention. A content analysis of the same dataset yielded information about preferred places in the community, promotion through churches, a tolerable price, and the balance class product itself. The qualitative results will inform the social marketing program to increase intervention delivery success.

Safety practices in relation to home ownership among urban Mexican immigrant families.

UNLABELLED: We examined home safety hazards, comparing renter- to owner-occupied housing among urban, immigrant Mexican families. METHODS: Interviews and home inspections were conducted among urban, Spanish-speaking immigrant families with children. We estimated weighted hazard prevalence and used logistic regression to compare owner- and renter-occupied homes. Of 313 eligible households, 250 (80%) enrolled. Respondents were predominantly Mexican-born (99%), low income (72.6%) and lower education (92.3%). Most homes had fire, burn, fall, poisoning, electrocution and fire escape hazards, including high tap water temperatures (76.4%; 95% CI: 69.0, 83.7%), no working smoke alarms (60.0%; 51.3, 68.8%), slippery bathtub/shower surfaces (58.7%; 49.9, 67.5%), blocked fire escape routes (55.9%; 47.2, 64.5%) and child-accessible medications (71.0%; 60.1, 81.3%). After adjustment for sociodemographics, fire escape (OR = 8.8; 95% CI: 2.8, 27.7), carbon monoxide poisoning (OR = 2.9; 1.4, 6.2) and drowning (OR = 3.5; 1.3, 9.4) hazards were more likely in owner- than renter-occupied homes. Housing age and type explained most differences. Many urban, immigrant Spanish-speaking families live in unsafe homes. For this population, housing safety programs should be targeted based on housing age and type rather than tenure.

Sickness behaviors following medial frontal cortical contusions in male rats.

Behaviors associated with sickness (food consumption, weight maintenance, exploratory activity and grooming frequency) were examined on post-surgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4 mg/kg) and/or vehicle. Rats with medial frontal cortex contusions showed reduced food consumption on days 1 and 3 (p < 0.01), reduced weight maintenance on days 1, 3, 5, 7 and 9 (p < 0.01), reduced grooming frequency on day 1 (p < .01), and reduced exploratory activity on day 1 (p < 0.01), after injury compared to sham rats. Contusion induced behaviors were not attenuated with 5 days of progesterone treatment (p > 0.05). Progesterone did reduce lesion size at 9 days after injury (p < 0.05). Our results suggest sickness behaviors occur after traumatic brain injury and that they might not respond to some neurosteroidal agents.

Increased police patrols for preventing alcohol-impaired driving.

BACKGROUND: Road traffic injuries cause 1.2 million deaths worldwide each year. Alcohol consumption increases the risk of traffic crashes, especially fatal crashes. Increased police patrols aim to increase both the perceived and actual likelihood of being caught driving while alcohol-impaired, potentially reducing alcohol-related driving, crashes and injuries. OBJECTIVES: To assess the effects on injuries and crashes of increased police patrols that target alcohol-impaired driving. SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register (5/2006), CENTRAL (The Cochrane Library 2006, Issue 2), MEDLINE (1966 to 5/2006), TRANSPORT (1968 to 5/2006), C2-SPECTR (2/2005), NCJRS (1/1951 to 5/2006), PsycINFO (1872 to 5/2006), Social Science Citation Index (1974 to 5/2006), SIGLE (1980 to 2/2006), Science Citation Index Expanded (1970 to 5/2006), Dissertation Abstracts (1870 to 5/2006), NTIS (1964 to 12/2004), conference proceedings, and reference lists. We contacted authors of eligible studies. SELECTION CRITERIA: Randomized controlled trials, controlled trials, controlled before and after studies, interrupted time series (ITS) studies, and controlled ITS studies evaluating increased police patrols, either alone or combined with other interventions, targeting alcohol-impaired motor vehicle drivers. DATA COLLECTION AND ANALYSIS: Two investigators independently screened citations, extracted data, and assessed quality criteria. We compared intervention and no-intervention geographical areas or time periods. We re-analyzed study data as required. Results are presented narratively. MAIN RESULTS: The 32 eligible studies included one randomized controlled trial, eight controlled before-after studies, 14 controlled ITS studies, six ITS studies, and three studies with both ITS and controlled before-after analyses. Most interventions targeted only alcohol-impaired driving (69%) and included additional interventions such as media campaigns or special training for police officers (91%). Only two studies reported sufficient information to assess study quality completely. Two-thirds of studies were scored 'not adequate' on at least one feature. Five of six studies evaluating traffic fatalities reported reductions with the intervention, but differences were statistically significant in only one study. Effects of intervention on traffic injuries were inconsistent in the six studies evaluating this outcome, and no results were statistically significant. All four controlled studies evaluating fatal crashes reported reductions with the intervention, which were statistically significant in one study. All 12 controlled studies assessing injury crashes reported greater reductions with the intervention, though effects were minimal or not significant in several studies. ITS studies showed less consistent effects on fatal crashes (three studies) and injury crashes (four studies), and effect estimates were typically imprecise. Thirteen of 20 studies showed reductions in total crashes and about two-thirds of these were statistically significant. AUTHORS' CONCLUSIONS: Studies examining increased police patrol programs were generally consistent in reporting beneficial effects on traffic crashes and fatalities, but study quality and reporting were often poor. Methodological limitations included inadequate sample size, dissimilar baseline measures, contamination, and inadequate data analysis. Thus existing evidence, although supportive, does not firmly establish whether increased police patrols, implemented with or without other intervention elements, reduce the adverse consequences of alcohol-impaired driving.

Effects of progesterone on the inflammatory response to brain injury in the rat.

The effects of progesterone on the cellular inflammatory response to frontal cortex injury were examined on postsurgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4 mg/kg) and/or vehicle. Rats with bilateral contusions showed increased levels of edema on days 1, 3 and 5, more reactive astrocytes on days 3, 5, 7 and 9, and more macrophages/activated microglia on days 1, 3, 5 and 9 compared to shams. The number of neurons in the medial dorsal nucleus (MDN) of the thalamus reduced on days 5 and 9 after injury compared to shams. Progesterone reduced edema levels and increased the accumulation of macrophages/activated microglia compared to vehicle controls (p<0.025); however, these changes in the inflammatory response were not related to MDN neuronal survival. Our results confirm the possibility that one way progesterone mediates its neuroprotective effects following injury is through its actions on the inflammatory response.

Behavioral effects and anatomic correlates after brain injury: a progesterone dose-response study.

Evidence suggests that progesterone enhances functional recovery in rats after medial frontal cortical contusions; however, a high dose of progesterone exacerbates tissue loss in a stroke model when administered chronically (7-10 days) prior to injury [Stroke 31 (2000) 1173)]. This study attempts to determine progesterone's dose-response effects on behavioral performance and GABA-A receptor expression following a cortical contusion. Male rats received injections of 0, 8, 16, or 32 mg/kg progesterone in 22.5% 2-hydroxypropyl-beta-cyclodextrin following cortical impact. Lesion 8 mg/kg and lesion 16 mg/kg groups displayed less thigmotaxis in the Morris water maze (MWM) than 0 and 32 mg/kg groups and were not significantly impaired relative to shams on other water maze measures. Increased variability in the 32 mg/kg group during somatosensory neglect testing was the only evidence indicating that a high dose of progesterone was disruptive to a few animals. These results suggest that low and moderate doses of progesterone are optimal for facilitating recovery of select behaviors and that postinjury progesterone treatment permits a wider dose range than preinjury treatment. Progesterone did not affect lesion size, but a strong negative correlation was observed between thalamic GABA-A receptor density and water maze performance. Future studies could explore causes for this relationship.