Re: External Carotid Artery Territory Ischemia Impairs Outcome in the Endovascular Filament Model of Middle Cerebral Artery Occlusion in Rats

Abstract

We read with interest the article by Dittmar et al 1 on body weight loss after middle cerebral artery occlusion (MCAO) by the intraluminal filament method. The authors provided evidence that transection of the external carotid artery (ECA), which is necessary for thread insertion, produced ischemic tissue damage of the lingual and pharyngeal musculature leading to impaired mastication and swallowing functions and eventually loss of body weight. Loss of body weight, however, was also severe in rats subjected to MCAO with no evidence of damage in the ECA territory, suggesting that other factors are involved.We have investigated whether dehydration, postoperative stress, or altered hormonal secretion contribute to body weight loss after 120 minutes MCAO ( Figure). 2 Based on plasma osmolality measurements (OSMOL), our rats were not dehydrated, perhaps due in part to the supplemental 0.9% NaCl given to the rats. Corticosterone levels (CORT) were increased only transiently after MCAO, indicating that extensive surgical procedures and postoperative stress do not contribute to weight loss. Unilateral damage to the hypothalamus is typical in MCAO rats and might contribute to postoperative hyperthermia, 3 but according to our data this does not affect plasma thyroid-stimulating hormone (TSH). Thus, it is unlikely that thyroid-mediated alterations in cellular metabolic activity account for the loss of body weight. The only long-lasting change, which parallels the loss of body weight (Ϫ20%), was a decrease in plasma leptin (LEPTIN). This might be a compensatory response that protects the body from starvation, however, rather than the reason for the body weight loss.Given that loss of body weight was also severe in rats subjected to MCAO with no evidence of damage in the ECA territory, the minimal postoperative weight loss in sham-operated rats with the ECA transection, 1 and body weight loss in MCAO models with no surgical manipulation of the ECA, 4 the most likely explanation for weight loss in MCAO rats is the extensive corticostriatal damage per se. We agree that there is a need to continue to develop stroke models to provide more accurate and clinically relevant data, but it is also important to ensure the general welfare of experimental animals. The early MRI investigation recommended by Dittmar et al, 1 however, is not feasible for large-scale studies. Instead, we recommend (1) careful monitoring of postoperative weight loss, (2) Response: Determinants of Body Weight Changes in the MCAO Filament ModelFirst of all we would like to thank Drs Virtanen, Sivenius, and Jolkkonen for their inspiring comments on our recent article, 1 and we would like to discuss their considerations as far as our work is concerned.Monitoring of body weight after surgery for intraluminal middle cerebral artery occlusion (MCAO) is an important measure to evaluate the general physiological condition of experimental rats. It is beyond controversy that several causal factors are involved in postoperative weight loss. Obviously, anesthesia and th...

Glibenclamide in Cerebral Ischemia and Stroke

“…tMCAo in rats is associated with severe weight loss of unknown etiology that is not explained by dehydration, stress, or altered hormonal secretions [42–44]. In the aformentioned study [17], weight gain quickly resumed its normal trajectory and endured for the 2 weeks of observation in the rats treated with glibenclamide, but not in those treated with decompressive craniectomy.…”

A microsurgical procedure for middle cerebral artery occlusion by intraluminal monofilament insertion technique in the rat: a special emphasis on the methodology

“…This causes hypothalamic infarction with associated pathologic hyperthermia that confounds the results of the investigation, for instance neuroprotective drug evaluation [6,38,42]. Finally, the anterior choroidal artery can be occluded by the filament, while the lumen of the MCA still allows perfusion.…”

Experimental approaches to study functional recovery following cerebral ischemia

“…The filament model is compromised by the poor health of the animal due to loss of body weight [68][69][70], postoperative stress, hyperthermia [71,72] and immunodepression and peripheral infections [20,73], which all affect behavioral outcome. Interestingly, stroke patients are also susceptible to many of these complications, and they have a substantial effect on outcome and often impede functional recovery [74].…”

“…Although other factors such as the extensive corticostriatal damage per se are likely to contribute to the body weight loss [69], special care is needed to overcome this complication and to improve the overall condition of rats. Importantly, feeding difficulties and loss of body weight complicate all food-rewarded behavioral tasks.…”