Effects of dexamethasone and progesterone treatment on experimental brain injury induced by surgical electrocautery

Abstract

Haemostasis is an important aspect in neurosurgical operations for the achievement of good outcome. Bipolar coagulation is an extensively used haemostatic technique in modern neurosurgery but it may also cause iatrogenic brain trauma due to thermal injury. Published studies on coagulation-induced brain injury on a histological level are, however, limited. The present study aimed at investigating the extent of inflammatory and glial responses caused by different settings of bipolar coagulation using an animal model. It also investigated whether and how pre-operative treatment with dexamethasone or progesterone, both known to have neuro-protective effects, would modulate gliosis and macrophage infiltration induced by bipolar coagulation.

The study consisted of two parts. The first part investigated the astrocytic and macrophage responses after bipolar coagulation at different power settings. 45 Sprague-Dawley rats received craniotomy, followed by bipolar coagulation at different power output settings (mock operation as control, 20W and 40W) over the rat cortex for a standardized duration of two seconds. On day 3, day 7 and day 28, brain sections were assessed by immunohistochemical staining for GFAP (astrocytes) and ED1 (macrophages). Quantification of outcome by random field cell counting under light microscopy was performed.

The second part of the study used another 45 male Sprague-Dawley rats, divided into three treatment groups: Group 1 received the vehicle agents only (Control); Group 2 received progesterone 20mg/kg; Group 3 received dexamethasone 1 mg/kg. All treatments were given intraperitoneally two hours before craniotomy. The animals received bipolar coagulation at 40W for a standardized duration of two seconds. On day 1, 3 and 7, brain sections were assessed by immunohistochemical staining for GFAP and ED1. Quantification of outcome by random field cell counting under light microscopy was performed. T2-weighted magnetic resonance imaging for the animals on day 3 was also performed.

The results showed that bipolar coagulation was associated with significant glial and inflammatory responses that correlated with power output. Progesterone and dexamethasone were both effective in reducing the glial hypertrophy and macrophage infiltration associated with bipolar coagulation. Dexamethasone had an additional advantage of reducing brain oedema and cavity formation. The findings suggested that progesterone and dexamethasone could be further explored as potential protective and/or remedial agents for bipolar coagulation-induced brain trauma sustained during neurosurgical procedures.