Lin Kooi Ong, PhD

Yang J, Kim E, Beltran C, Cho S. Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival. Stroke. 2019;50:2539–2546.

“Stress is bad for you, right? Well, not necessarily. The devil is in the dose, and how you perceive the stress.”1
—Dr. Lila Landowski, University of Tasmania

In response to stroke, the hypothalamic-pituitary-adrenal axis is activated and releases glucocorticoids such as cortisol. Cortisol is involved in stress responses, regulation of energy and immune reactions. Yang et al. aimed to elucidate the acute actions of corticosterone in body weight loss, immunity responses and survival after experimental stroke in mice. Corticosterone is a major catabolic steroid hormone produced from the adrenal gland in rodents (cortisol in humans). The team observed a small burst of corticosterone levels around 1 to 3 hours and decreased back to baseline around 6 hours after stroke. Further, they noted that the degree of weight loss at day 3 estimates the severity of the stroke as well as the infiltration of peripheral immune cells into the brain. As the role of corticosterone during the acute stroke phase is controversial, the team tested the concept by surgically removing the adrenal glands prior to induction of experimental stroke. All mice with intact adrenal glands survived after stroke, and only 1 out of 8 mice following adrenalectomy survived. Interestingly, treating adrenalectomy mice with corticosterone partially rescued the survival rate to 4 out of 10. Based on the findings, the authors suggested that the adrenal corticosterone-mediated catabolic process is necessary for poststroke immunity and survival.

In contrast, a major problem that interferes with brain recovery after stroke is ongoing stress (and high levels of stress hormone – cortisol). We and other groups have provided extensive pre-clinical evidence that chronic stress during stroke recovery promotes loss of neurons and accumulation of neurotoxic proteins, as well as inhibits brain repair processes, leading to poorer outcomes.2,3,4 Collectively, the hypothalamic-pituitary-adrenal axis may represent a potential target to limit the detrimental effects associated with chronic stress. However, consideration should be given on how long after the initial stroke to initiate the treatment, in order to avoid diminishing the acute actions described by Yang and colleagues.


1. Landowski L. Trying to boost your brain health with sudoku, sugar or even sex? Let’s take a look at the evidence. ABC Health & Wellbeing. 2019; Retrieved from

2. Ong LK, Zhao Z, Kluge M, Walker FR, Nilsson M. Chronic stress exposure following photothrombotic stroke is associated with increased levels of Amyloid beta accumulation and altered oligomerisation at sites of thalamic secondary neurodegeneration in mice. J Cereb Blood Flow Metab. 2017; 37:1338-1348.

3. Zhao Z, Ong LK, Johnson S, Nilsson M, Walker FR. Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke. J Cereb Blood Flow Metab. 2017; 37:3709-3724.

4. Zalewska K, Pietrogrande G, Ong LK, Abdolhoseini M, Kluge M, et al. Sustained administration of corticosterone at stress-like levels after stroke suppressed glial reactivity at sites of thalamic secondary neurodegeneration. Brain Behav Immun. 2018; 69:210-222.