Potential for thermal damage to the blood-brain barrier during craniotomy: implications for intracortical recording microelectrodes

Abstract

Objective: Our objective was to determine how readily disruption of the blood-brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature.

Approach: We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1 h after the craniotomy procedure using Evans blue dye.

Main results: Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from +3 °C to +21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation.

Significance: Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during 'off' periods. While saline alone was ineffective at preventing overheating, its use is still recommended to remove bone dust from the surgical site and to augment other cooling methods.

Figure 1:. Literature review of rodent craniotomy methods.

479 journal articles were identified from a PubMed database search that included a search for rodent (rat or mouse) craniotomy methods, as well as all papers pertaining to “intracortical microelectrodes”. Column 1: articles were categorized by their primary field of publication (e.g., “trauma” vs “orthopedics”). Column 2: of the subset of journal articles pertaining to “intracortical microelectrodes” (n=61), 89% did not specifically mention methods for the prevention of drill overheating during craniotomy; 38% provided no details regarding the craniotomy method whatsoever. Column 3: of the subset of intracortical microelectrode papers that described a method to prevent drill overheating (n=7), 4/7 described the use intermittent saline, 2/7 described the use of continuous saline irrigation, and 1/7 described the use of an alternative method for producing the craniotomy, i.e., a biopsy punch.

Figure 2:. Maximum temperature recorded during drilling of rat craniotomy.

To quickly visualize whether we were overheating the skull during drilling, we captured thermal images of the drilling with an infrared camera. Maximum temperatures exceeded an increase of +21 °C from baseline for the 15k revolutions per minute (RPM) drill speed. The image shown was captured using a thermal infrared camera to show the temperature profile of the skull surface. A picture was taken for 1k, 5k, 10k, and 15k RPM, which increased the baseline temperature by +3°C, +5°C, +8°C, and +21°C, respectively.

Figure 3:. Transient temperature changes at the brain surface during 15k RPM drilling (directly below the post mortem rat skull).

We placed a small thermocouple on the brain surface from a secondary hole previously drilled ~2 mm away from the site (figure inlay). The experiment was performed with post mortem tissue as placement of the thermocouple was likely to cause damage to the superficial surface of the brain during placement therefore making in vivo measurement impractical. Three types of drilling at 15k RPM were tested (continuous, pulsed 2s-on/2s-off, and pulsed 2s-on/5s-off) in triplicate (n=3 per condition). We observed that continuous application of the drill led to temperature increases greater than 25°C within 15–30s. Pulsed application still led to a significant increase in temperature (ranging from +9.1 to +13.6°C). Further extending the “off” period duration to 5s during pulsed application of the drill to allow for additional cooling resulted in (+3.1 to +7.9°C). In all tested cases, the brain cooled down back to baseline within 60s from peak temperature.

Figure 4:. Evans blue dye concentration 1-hour after performing various powered drill craniotomy techniques.

We measured Evans blue concentrations after drilling at various speeds (15k, 10k, 5k, 1k RPM) as well as either continuously or pulsed 2s-on/2-s off. There was a nearly 15-fold increase in dye concentration in the brain tissues that were exposed to continuous 10k or 15k speed drilling versus the “no drill” control. Slow speed (1k) and pulsed application appear to be the most effective means to reduce impacts on BBB permeability. Interestingly, saline application was not an effective or repeatable method to mitigate increases in BBB permeability from 15k continuous drilling. n=11 for 15k and “no drill” conditions; n=4 per group for 10k, 5k, 1k, “15k pulsed”, and “15k saline” conditions. Bars represent mean +/− standard error of the mean. Analysis included ANOVA with pairwise comparisons with Tukey tests: *p<0.05; **p<0.01; ***p<0.001