Table 3.

Effect of Cancer Treatment on Neurobiobehavioral Status in Rodents

Study	Origin of Specimen(s)	Treatment	Effect on Neurons/Cognition	Comments/Limitations
Ordy et al,26 1963	50 female mice, 10 controls	80–720 Gy to various brain areas	Difference in mean overall scores of open-field latency between subjects and controls. Beginning in month 5, bilateral parietal CRT group scored highera on open-field latency. Right cerebellar CRT group significantly slower on locomotor wheela	Very early study relating CRT to behavior changes. Delayed behavioral effects on mice after radiation may be due to necrosis, vascular damage after high doses of radiation
Rao et al,27 2011	1-mo-old male mice and controls	4-Gy WBRT for 5 consecutive days	Impairment of nonspatial learning at 1 mob and 5 moa post-CRT	First study to demonstrate continued ↓ in memory behavior long-term after early fractionated CRT to young rodents.
Rola et al,28 2004	Twenty-four 21-d-old mice; 12 subjects, 12 controls	5-Gy WBRT to subjects, controls sham-irradiated	Irradiated mice had deficits in memory retention 3 mo after WBRT,a greater numbers of immature neurons after behavioral training than nonirradiated micea	Increased immature neurons in behaviorally trained mice after WBRT likely due to learning-enhanced survival rather than physical activity of training, may lead to improved cognitive functioning. Limitation: single-dose radiation not representative of pediatric therapy
Seigers et al,54 2008	Adult male rats	HD-MTX 250 mg/kg, controls received saline	Animals treated with MTX: longer latency timeb for spatial memory. Control rats had better novel recognitionb	Longer latency time indicates impaired spatial memory, failure to distinguish familiar object from novel reflects ↓ HC functioning
Seigers et al,55 2009	Adult male rats	HD-MTX 250 mg/kg, controls received saline	Rats treated with MTX spent less time in platform quadrant,b had less freezing behavior, indicating fearc	Results from both tests indicate retrograde amnesia, impaired memory consolidation after learning specific behaviors, due to MTX
Winocur et al,56 2006	25 female adult mice	MTX 37.5 mg/kg IP and 5-fluorouracil 75 mg/kg IP each week for 3 wk. Control mice given IP saline injections	Chemo-treated mice had longer latencies, more errors on spatial memory testing on day 1, but similar to controls as time went on. On delayed NMTS, chemo group had treatment × delay interaction on latencyc and errorc scores	Spatial memory, conditional rule learning, longest delay of nonspatial memory test affected by chemo. Limitations: with administration of 2 drugs, cannot ascribe effects to either. Differences in spatial memory could be attributed to hyperarousal or hyperactivity

Abbreviations: CRT, cranial radiation therapy; HC, hippocampus; HD, high-dose; IP, intraperitoneal; MTX, methotrexate; NMTS, nonmatching to sample learning; WBRT, whole-brain radiation therapy.

^aP < .01.

^bP < .05.

^cP < .001.