Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair. However, its continued activation is highly detrimental and a common final pathway of numerous disease states including cardiovascular and respiratory disease. Worldwide, fibrotic diseases cause over 800,000 deaths per year, accounting for ~45% of total deaths. With an aging population, the incidence of fibrotic disease and subsequently the number of fibrosis-related deaths will rise further. Although, fibrosis is a well-recognized cause of morbidity and mortality in a range of disease states, there are currently no viable therapies to reverse the effects of chronic fibrosis. Numerous predisposing factors contribute to the development of fibrosis. Biological aging in particular, interferes with repair of damaged tissue, accelerating the transition to pathological remodeling, rather than a process of resolution and regeneration. When fibrosis progresses in an uncontrolled manner, it results in the irreversible stiffening of the affected tissue, which can lead to organ malfunction and death. Further investigation into the mechanisms of fibrosis is necessary to elucidate novel, much needed, therapeutic targets. Fibrosis of the heart and lung make up a significant proportion of fibrosis-related deaths. It has long been established that the heart and lung are functionally and geographically linked when it comes to health and disease, and thus exploring the processes and mechanisms that contribute to fibrosis of each organ, the focus of this review, may help to highlight potential avenues of therapeutic investigation.

We saw major intracranial pressure elevation 24 h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18 h after rewarming. The findings have potentially important implications for design of future clinical trials.

In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equates to higher ICP. We recently demonstrated a dramatic ICP elevation 24 hours after small ischemic strokes in rats, with minimal edema. This ICP elevation was completely prevented by short-duration moderate hypothermia soon after stroke. Here, our aims were to determine the importance of edema in ICP elevation after stroke and whether mild hypothermia could prevent the ICP rise. Experimental stroke was performed in rats. ICP was monitored and shortduration mild (35°C) or moderate (32.5°C) hypothermia, or normothermia (37°C) was induced after stroke onset. Edema was measured in three studies, using wet-dry weight calculations, T 2 -weighted magnetic resonance imaging, or histology. ICP increased 24 hours after stroke onset in all normothermic animals. Short-duration mild or moderate hypothermia prevented this rise. No correlation was seen between ΔICP and edema or infarct volumes. Calculated rates of edema growth were orders of magnitude less than normal cerebrospinal fluid production rates. These data challenge current concepts and suggest that factors other than cerebral edema are the primary cause of the ICP elevation 24 hours after stroke onset.