Beyond border health: Infrastructural violence and the health of border abolition.

Most existing approaches to border health focus on identifying the social determinants that produce ill health and health disparities among migrants, including language barriers, documentation status, and trauma associated with migration. Attention to these kinds of problems can lead to policy and clinical changes that indeed help improve quantitatively measurable outcomes for patients. However, these approaches usually ignore the larger historical and political framework that determines the determinants - the underlying infrastructure of ill health, or what we term the infrastructural determinants of health. In this paper, we outline specific infrastructures involving race, political economy, history, and most importantly, borders themselves, that lay the foundations for border illness. We examine the plans, histories, policies, and peoples involved in building the conditions for migration, particularly out of the Northern Triangle, including forces of colonialism, US imperialism, neoliberalism, and border militarization. In place of a tacit acceptance of the modern system of borders, we argue for border abolition as a vital but underused treatment in the repertoire of medical intervention. Outlining the rights of people to stay and to move, and drawing on lessons from the prison abolition movement, we offer policies and practices towards a 'no borders' system that privileges liberatory solidarity with migrants by explicitly challenging global infrastructures that drive displacement. In doing so, we offer an emergent framework for a medical border abolition that treats both the causes and symptoms of a widespread global sickness.

Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death.

Estradiol enhances plasticity and survival of the injured brain. Our previous work demonstrates that physiological levels of estradiol protect against cerebral ischemia in the young and aging brain through actions involving estrogen receptors (ERs) and alterations in gene expression. The major goal of this study was to establish mechanisms of neuroprotective actions induced by low levels of estradiol. We first examined effects of estradiol on the time-dependent evolution of ischemic brain injury. Because estradiol is known to influence apoptosis, we hypothesized that it acts to decrease the delayed phase of cell death observed after middle cerebral artery occlusion (MCAO). Furthermore, because ERs are pivotal to neuroprotection, we examined the temporal expression profiles of both ER subtypes, ERalpha and ERbeta, after MCAO and delineated potential roles for each receptor in estradiol-mediated neuroprotection. We quantified cell death in brains at various times after MCAO and analyzed ER expression by RT-PCR, in situ hybridization, and immunohistochemistry. We found that during the first 24 h, the mechanisms of estradiol-induced neuroprotection after MCAO are limited to attenuation of delayed cell death and do not influence immediate cell death. Furthermore, we discovered that ERs exhibit distinctly divergent profiles of expression over the evolution of injury, with ERalpha induction occurring early and ERbeta modulation occurring later. Finally, we provide evidence for a new and functional role for ERalpha in estradiol-mediated protection of the injured brain. These findings indicate that physiological levels of estradiol protect against delayed cell death after stroke-like injury through mechanisms requiring ERalpha.

Tat-calpastatin fusion proteins transduce primary rat cortical neurons but do not inhibit cellular calpain activity.

Excessive activation of calpains (calcium-activated neutral proteases) is observed following spinal cord contusion injury, traumatic brain injury, stroke, and in neurodegenerative disorders including Alzheimer's disease. Calpain inhibition represents an attractive therapeutic target, but current calpain inhibitors possess relatively weak potency, poor specificity, and in many cases, limited cellular and blood-brain barrier permeability. We developed novel calpain inhibitors consisting of the endogenous inhibitor, calpastatin or its inhibitory domain I, fused to the protein transduction domain of the HIV trans-activator (Tat) protein (Tat(47-57)). The Tat-calpastatin fusion proteins were potent calpain inhibitors in a cell-free activity assay, but did not inhibit cellular calpain activity in primary rat cortical neurons when applied exogenously at concentrations up to 5 microM. The fusion proteins were able to transduce neurons, but were localized within endosome-like structures. A similar endosomal uptake was observed for Tat-GFP. Together, the results suggest that endosomal uptake of the Tat-calpastatin prevents its interaction with calpain in other cellular compartments. Endosomal uptake of proteins fused to the Tat protein transduction domain severely limits the applications of this methodology.