Diet-induced obesity causes cerebral vessel remodeling and increases the damage caused by ischemic stroke

Abstract

Hypertension, elevated fasting blood glucose and plasma insulin develop in rats fed a high fat (HF) diet. Our goal was to assess the effects of obesity, beginning in childhood, on the adult cardiovascular system. We hypothesized that rats fed a HF diet would have larger ischemic cerebral infarcts and middle cerebral artery (MCA) remodeling. Three-week-old male Sprague Dawley rats were fed a HF (Obese) or control diet for 10 weeks. Cerebral ischemia was induced by MCA occlusion (MCAO). MCA structure was assessed by pressure myography and cerebral vessel matrix metalloproteinase (MMP) activity and expression and collagen levels were measured in vessels from rats that did not undergo MCAO. The cerebral infarct was greater in the obese rats than the control (46.0±2.1 vs 28.0±7.5 percent of the hemisphere infarcted, obese vs control p<0.05). The MCAs from obese rats had smaller lumens (232±7.2 vs 254±7.8μm obese vs control p<0.05) and thicker walls (19.6±0.8 vs 17.8± 0.9μm obese vs control p<0.05) and were less compliant than MCAs from control rats. MMP-2 activity and collagen I expression were increased in vessels from obese rats and MMP-13 expression was reduced. These results suggest obesity, beginning in childhood, causes inward vessel remodeling with a concomitant increase in vessel stiffness due to increased collagen deposition. These changes in MCA structure may be responsible for the increase in the ischemic damage after MCAO.

Early effects of high-fat diet on neurovascular function and focal ischemic brain injury

“…Experimental studies have shown that either HFD or genetically induced obesity was accompanied by increased cerebrovascular remodeling, promoted hypertension, and increased infarct size in either transient or permanent focal ischemia models (7,32). HFD-fed apoEϪ/Ϫ mice with hyperlipidemia also had increased infarct volume (23).…”

“…Given that stroke is the leading cause of disability and that the obesity epidemic is on the rise these clinical and social problems are expected to get worse, and therefore early interventions are necessary. While experimental studies in genetic or diet-induced obesity models have shown increased cerebral infarct size and poor outcomes of stroke (7,25,32,33,41), the early impact of a high-fat diet (HFD) before the development of obesity on AIS injury and functional outcomes is not known.It is known that the brain relies heavily on constant blood flow for proper function. Two important mechanisms that contribute to the regulation of cerebral blood perfusion are autoregulatory behavior of cerebral vessels and functional hyperemia upon increased neuronal activity (11,16,20).…”

“…Given that stroke is the leading cause of disability and that the obesity epidemic is on the rise these clinical and social problems are expected to get worse, and therefore early interventions are necessary. While experimental studies in genetic or diet-induced obesity models have shown increased cerebral infarct size and poor outcomes of stroke (7,25,32,33,41), the early impact of a high-fat diet (HFD) before the development of obesity on AIS injury and functional outcomes is not known.…”

“…Two important mechanisms that contribute to the regulation of cerebral blood perfusion are autoregulatory behavior of cerebral vessels and functional hyperemia upon increased neuronal activity (11,16,20). HFD can negatively affect vascular function, as demonstrated by increased myogenic tone and endothelial dysfunction in dietinduced as well as genetic models of obesity (7,8,24,32,33). The effect of a HFD on neurovascular coupling and cerebrovascular reactivity after an ischemic insult especially in the absence of metabolic abnormalities is unknown.…”

Maternal high-fat diet influences stroke outcome in adult rat offspring

“…Nevertheless, other studies have also reported that adult offspring of HFD-fed dams can have normal glucose tolerance and body composition (Miotto et al 2013, Platt et al 2014. More specifically, although numerous studies have indicated the cerebrovascular hazards of an increased intake of dietary fat in adults (Langdon et al 2011) or beginning in childhood (Deutsch et al 2009), it remains to be established whether HFD consumption during pregnancy and the suckling period can influence the cerebrovascular health of adult offspring.…”